Method of microencapsulating an agricultural active having a high melting point and uses for such materials

ABSTRACT

A method of producing a controlled release form of an agricultural active material includes the provision of an organic liquid composition in which the active is present, but where the liquid composition is free from aromatic solvents and is maintained below the normal melting point of the active. The liquid composition is formed into small droplets and the droplets are enclosed by a non-water soluble shell to provide microcapsules, the shell of which is designed to release the agricultural active at a pre-selected controlled rate when the microcapsule is exposed to natural environmental conditions. Controlled release forms of agricultural actives are also provided.

BACKGROUND OF THE INVENTION

(1) Field of the Invention

The present invention relates to methods for the microencapsulation ofan agricultural active having a high melting point, and moreparticularly to methods for the microencapsulation of such materialwhile maintaining the temperature of the agricultural active below itsnormal melting point and without contacting the active with an aromaticsolvent.

(2) Description of the Related Art

Materials that affect the growth and development of agronomicallyimportant plants, or that provide some type of protection of plants frompests and diseases, are commonly referred to as agricultural actives.Such materials are widely used in modern agriculture and providebenefits of increased yield, vigor and overall plant health. However,some agricultural actives have harmful effects if they are ingested orotherwise contacted by humans or other animals.

The most common method for using agricultural actives is directapplication of the active to a plant, seed, or to the soil in which theplant is to be grown. But wind, runoff and groundwater leaching cancause undesirable movement of the active, which can result in itsunintended contact with plants and animals in streams, neighboringfields and homes. Furthermore, such movement of the active from the zonewhere protection is desired can result in reduction of the concentrationof the active to below efficacious levels by the time the target pestarrives. Irreversible binding of the active to components of soilexacerbates this problem.

One method to improve the delivery and safety characteristics ofagricultural actives is to include them as components of a controlledrelease composition. Many different types of such controlled releasecompositions are known and include the encapsulation of droplets, theformation of a coating on solid particles, and the inclusion of activesin matrix microparticles. Such formulations typically place coatings ofa barrier material between the active and the environment through whichthe active must move in order to reach the environment. The rate atwhich such transfer takes place depends upon the type of coating, itsthickness, the chemical affinity of the active for the matrix, as wellas many environmental parameters, such as temperature, moisture levels,and the like.

Thus, encapsulation of an active can improve its safety and stability,its dispersibility and even distribution, its handling characteristics,as well as to control its release rate.

Although both solid particles and liquids can be enclosed in coatings,the formation of microcapsules around liquid droplets is believed tohave several advantages over the coating of solid particles. Forexample, microcapsules formed around liquid droplets have regularspherical geometry, coatings of even thickness, and lack sharp edges andconcave surfaces, which can occur in coatings of solid particles, andwhich could cause uneven coating thickness or even lack of a coating onsome parts of the active. A coating having a regular geometry and aneven thickness provides more predictable release characteristics than anuneven coating of varying thickness.

A number of methods for the encapsulation of liquid droplets containingagricultural actives is known in the art, and a summary of such methodsis provided, for example, in Controlled-Release Delivery Systems forPesticides, H. B. Scher, Ed., Marcel Dekker, Inc., New York (1999); inMicroencapsulation, S. Benita, Ed., Marcel Dekker, New York (1996); andin Microencapsulation and Related Drug Processes, Patrick B. Deasy, Ed.,Marcel Dekker, New York (1984).

Matson, in U.S. Pat. Nos. 3,516,846 and 3,516,941 and Sher et al., inU.S. Pat. No. 4,956,129, describe the formation of a urea-formaldehydepolymer coating around small liquid droplets.

Another commonly used method for the encapsulation of liquid dropletsinvolves the generation of a polyurea shell around an active-containingcore by interfacial polymerization at the surface of the droplets.Advantages of using a polyurea shell include that the material isgenerally non-phytotoxic, its permeability characteristics can becontrolled, and the shell can be formed at relatively lowtemperatures—in fact, polymerization temperatures of lower than 90° C.are almost always used, and temperatures of from about 40° C.-70° C.,are preferred.

In U.S. Pat. Nos. 4,285,720 and 4,643,764, Scher describes a processinvolving the blending of various pesticides with an organicpolyisocyanate to form an organic phase, which is dispersed into smalldroplets into an aqueous phase. Some molecules of the organicpolyisocyanate hydrolyze to form amines, which then can react with otherisocyanates to form the polyurea shell.

Chao, in U.S. Pat. No. 4,599,271, describes the use of two or moreorganic-in-aqueous emulsions for the formation of a polyurea shellaround a polyisocyanate containing droplet.

Beestman (in U.S. Pat. No. 4,640,709) discloses the inclusion of analkylated polyvinyl pyrrolidone polymer that acts as an emulsifier inthe aqueous phase of a two-phase system which is capable of providingmicrocapsules having high levels of an enclosed water-immisciblematerial.

In U.S. Pat. No. 4,681,806, Matkan et al. describe particles containinga releasable fill material and having a polyurea surface layer thatencloses a polyurea matrix having the fill material contained therein.

Ohtsubo et al. (in U.S. Pat. No. 4,889,719) describe themicroencapsulation of organophosphorous insecticidal compositions by theformation of a polyurea shell. Similar methods have been used for themicroencapsulation of herbicidally activeN-chloroacetylcyclohexeneamines and herbicidally activechloroacetanilide in a polyurea shell, and are described in U.S. Pat.No. 5,006,161, to Hasslin et al.

In U.S. Pat. No. 4,738,898, Vivant describes microencapsulation of avariety of materials within polyurea skin membranes by interfacialpolyaddition involving a polyisocyanato hydrophobic liquid in anessentially aqueous medium. The polyisocyanato hydrophobic liquidcontained the dissolved material to be encapsulated, an aliphaticdiisocyanate and an isocyanurate ring trimer of an aliphaticdiisocyanate. The isocyanate materials were reacted with a polyamine toform a polyurea shell material. The microcapsules described by Vivanthad leakproof walls that were designed for the microencapsulation ofcolorants and the production of pressure-sensitive carbonless paper, forexample. The microcapsules were designed to maintain the encapsulatedmaterial until the capsule was ruptured, and would not have beensuitable for the controlled release of the encapsulated materialsthrough the walls of the capsule.

Hasslin et al. (in U.S. Pat. No. 4,938,797) describes the encapsulationof a water-immiscible pesticide in a polyurea shell. The method includesthe use of an anionic dispersant, such as a salt of polystyrenesulfonicacid in the aqueous phase. A similar method is described in U.S. Pat.No. 5,310,721, to Lo, but all of the agricultural active materials thatare encapsulated are liquids at ambient temperature.

Seitz et al. (in U.S. Pat. No. 5,925,595) disclose a process for thepreparation of microencapsulated materials—including low-meltingherbicides, such as acetanilides—by combining a triisocyanate and adiisocyanate with a water immiscible composition which can include theherbicide; forming a dispersion of the core chemical and the blend ofisocyanates in an aqueous liquid; and reacting the isocyanates with apolyamine to form microcapsules.

In U.S. Pat. No. 6,133,197, Chen et al., describe the formation of quickrelease microcapsules containing an agriculturally active material andhaving a polyurea shell with relatively low degree of cross-linking.

Despite the advantages provided by microcapsules having polyurea shellsthat enclose liquid cores containing agricultural actives, the methodsthat are known for the formation of these structures have certainlimitations that limit their use with certain highly promising actives.For example, if the agricultural active has a melting point that isclose to, or higher than, the preferred range of polymerizationtemperature for polyurea shell formation, it is difficult to liquify theactive in order to form the microcapsule. A common solution to thissituation has been to dissolve the active in an aromatic solvent. See,e.g., WO 00/27200, where the formation of a slow release capsulesuspension is described wherein a mixture of a fungicide(thienol[2,3-d]pyrimidin-4-one) and another agricultural active(selected from a list of possible materials) is blended withpolyisocyanates in an aromatic solvent. This organic phase is emulsifiedin an aqueous liquid phase, and 1,6-diaminohexane is added to cause apolymerization reaction with the isocyanates to form microcapsules thatenclose the mixture of agricultural actives.

Since many aromatic solvents are phytotoxic, their use in controlledrelease formulations intended for application to plants or seeds wouldappear to be potentially harmful to the plant.

One new class of agricultural actives that appears to be very promisingfor fungicidal and other applications is described in U.S. Pat. Nos.5,482,974, 5,486,621, 5,498,630, 5,693,667, 5,693,667, 5,705,513,5,811,411, 5,834,447, 5,849,723, 5,994,270, 5,998,466, 6,028,101, and inpublications WO 93/07751, and EP 0 538 231 A1. One such compound, inparticular, is4,5-dimethyl-N-(2-propenyl)-2-(trimethylsilyl)-3-thiophenecarboxamide,having a CAS registration number of 175217-20-6, and for which theproposed ISO common name is “Silthiopham”. Silthiopham has a normalmelting point of about 86° C.-88° C., which has limited itsincorporation into polyurea microcapsules by known techniques. Furtherinformation about silthiopham can be found in U.S. Pat. No. 5,486,621.

Accordingly, it would be useful to provide a method for the formation ofmicrocapsules enclosing such high-melting agricultural actives where themethod was free of the use of aromatic solvents—and preferably free ofany solvents—and where the method could be carried out at a temperaturethat was below the normal melting point of the active. It would also beuseful if such method allowed for the use of a polyurea shell that couldbe designed to release the active from the microcapsule at a controlledrate when the microcapsule was exposed to natural environmentalconditions.

SUMMARY OF THE INVENTION

Briefly, therefore the present invention is directed to a novel methodof producing a controlled release form of a first agricultural activehaving a normal melting point, the method comprising providing anorganic liquid composition comprising a first agricultural active havinglow water solubility where the composition is free of aromatic solvents;forming the liquid composition into small droplets while maintainingsaid liquid composition at a temperature below the normal melting pointof the first agricultural active; and enclosing each droplet in anon-water soluble shell to form a microcapsule. When desired, the shellcan be designed to release the first agricultural active from themicrocapsule at a pre-selected controlled rate when the microcapsule isexposed to natural environmental conditions.

The present invention is also directed to a novel controlled releaseform of an agricultural active comprising a compound having the formula

-   -   wherein Z₁ and Z₂ are C or N and are part of an aromatic ring        selected from benzene, pyridine, thiophene, furan, pyrrole,        pyrazole, thiazole, and isothiazole;    -   A is selected from —C(X)-amine, —C(O)—SR₃, —NH—C(X)R₄, and        —C(═NR₃)—XR₇;    -   B is —W_(m)-Q(R₂)₃ or selected from o-tolyl, 1-naphthyl,        2-naphthyl, and 9-phenanthryl, each optionally substituted with        halogen or R₄; Q is C, Si, Ge, or Sn;    -   W is —C(R₃)_(p)H_((2-p))—; or when Q is C, W is selected from        —C(R₃)_(p) H_((2-p))—, —N(R₃)_(m)H_((1-m))—, —S(O)_(p)—, and        —O—;    -   X is O or S;    -   n is 0, 1, 2, or 3;    -   m is 0 or 1;    -   p is 0, 1, or 2;    -   each R is independently selected from    -   a) halo, formyl, cyano, amino, nitro, thiocyanato,        isothiocyanato, trimethylsilyl, and hydroxy;    -   b) C₁-C₄ alkyl, alkenyl, alkynyl, C₃-C₆ cycloalkyl, and        cycloalkenyl, each optionally substituted with halo, hydroxy,        thio, amino, nitro, cyano, formyl, phenyl, C1-C4 alkoxy,        alkylcarbonyl, alkylthio, alkylamino, dialkylamino,        alkoxycarbonyl, (alkylthio)carbonyl, alkylaminocarbonyl,        dialkylaminocarbonyl, alkylsulfinyl, or alkylsulfonyl;    -   c) phenyl, furyl, thienyl, pyrrolyl, each optionally substituted        with halo, formyl, cyano, amino, nitro, C₁-C₄ alkyl, alkenyl,        alkynyl, alkoxy, alkylthio, alkylamino, dialkylamino, haloalkyl,        and haloalkenyl;    -   d) C₁-C₄ alkoxy, alkenoxy, alkynoxy, C₃-C₆ cycloalkyloxy,        cycloalkenyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylamino, dialkylamino, alkylcarbonylamino, aminocarbonyl,        alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl,        alkylcarbonyloxy, alkoxycarbonyl, (alkylthio)carbonyl,        phenylcarbonylamino, phenylamino, each optionally substituted        with halo;    -   wherein two R groups may be combined to form a fused ring;    -   each R₂ is independently selected from alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl and phenyl, each optionally substituted        with R₄ or halogen; and wherein, when Q is C, R₂ may also be        selected from halo, alkoxy, alkylthio, alkylamino, and        dialkylamino;    -   wherein two R₂ groups may be combined to form a cyclo group with        Q;    -   R₃ is C₁-C₄ alkyl;    -   R₄ is C₁-C₄ alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or        dialkylamino;    -   R₇ is C₁-C₄ alkyl, haloalkyl, or phenyl, optionally substituted        with halo, nitro, or R₄; or an agronomic salt thereof.

The present invention is also drawn to a novel method of reducing themelting point of an agricultural active material having the formula

-   -   wherein Z₁ and Z₂ are C or N and are part of an aromatic ring        selected from benzene, pyridine, thiophene, furan, pyrrole,        pyrazole, thiazole, and isothiazole;    -   A is selected from —C(X)-amine, —C(O)—SR₃, —NH—C(X)R₄, and        —C(═NR₃)—XR₇;    -   B is —W_(m)-Q(R₂)₃ or selected from o-tolyl, 1-naphthyl,        2-naphthyl, and 9-phenanthryl, each optionally substituted with        halogen or R₄; Q is C, Si, Ge, or Sn;    -   W is —C(R₃)_(p)H_((2-p))—; or when Q is C, W is selected from        —C(R₃)_(p) H_((2-p))—, —N(R₃)_(m)H_((1-m))—, —S(O)_(p)—, and        —O—;    -   X is O or S;    -   n is 0, 1, 2, or 3;    -   m is 0 or 1;    -   p is 0, 1, or 2;    -   each R is independently selected from    -   a) halo, formyl, cyano, amino, nitro, thiocyanato,        isothiocyanato, trimethylsilyl, and hydroxy;    -   b) C₁-C₄ alkyl, alkenyl, alkynyl, C₃-C₆ cycloalkyl, and        cycloalkenyl, each optionally substituted with halo, hydroxy,        thio, amino, nitro, cyano, formyl, phenyl, C₁-C₄ alkoxy,        alkylcarbonyl, alkylthio, alkylamino, dialkylamino,        alkoxycarbonyl, (alkylthio)carbonyl, alkylaminocarbonyl,        dialkylaminocarbonyl, alkylsulfinyl, or alkylsulfonyl;    -   c) phenyl, furyl, thienyl, pyrrolyl, each optionally substituted        with halo, formyl, cyano, amino, nitro, C₁-C₄ alkyl, alkenyl,        alkynyl, alkoxy, alkylthio, alkylamino, dialkylamino, haloalkyl,        and haloalkenyl;    -   d) C1-C4 alkoxy, alkenoxy, alkynoxy, C₃-C₆ cycloalkyloxy,        cycloalkenyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylamino, dialkylamino, alkylcarbonylamino, aminocarbonyl,        alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl,        alkylcarbonyloxy, alkoxycarbonyl, (alkylthio)carbonyl,        phenylcarbonylamino, phenylamino, each optionally substituted        with halo;    -   wherein two R groups may be combined to form a fused ring;    -   each R₂ is independently selected from alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl and phenyl, each optionally substituted        with R₄ or halogen; and wherein, when Q is C, R₂ may also be        selected from halo, alkoxy, alkylthio, alkylamino, and        dialkylamino;    -   wherein two R₂ groups may be combined to form a cyclo group with        Q;    -   R₃ is C₁-C₄ alkyl;    -   R₄ is C₁-C₄ alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or        dialkylamino;    -   R₇ is C₁-C₄ alkyl, haloalkyl, or phenyl, optionally substituted        with halo, nitro, or R₄;    -   or an agronomic salt thereof, comprising mixing said        agricultural active material with tebuconazole or simeconazole.

The present invention is also directed to a novel controlled releaseform of an agricultural active comprising a compound having the formula

-   -   wherein Z₁ and Z₂ are C or N and are part of an aromatic ring        selected from benzene, pyridine, thiophene, furan, pyrrole,        pyrazole, thiazole, and isothiazole;    -   A is selected from —C(X)-amine, —C(O)—SR₃, —NH—C(X)R₄, and        —C(═NR₃)—XR₇;    -   B is —W_(m)-Q(R₂)₃ or selected from o-tolyl, 1-naphthyl,        2-naphthyl, and 9-phenanthryl, each optionally substituted with        halogen or R₄;    -   Q is C, Si, Ge, or Sn;    -   W is —C(R₃)_(p)H_((2-p))—; or when Q is C, W is selected from        —C(R₃)_(p) H_((2-p))—, —N(R₃)_(m)H_((1-m))—, —S(O)_(p)—, and        —O—;    -   X is O or S;    -   n is 0, 1, 2, or 3;    -   m is 0 or 1;    -   p is 0, 1, or 2;    -   each R is independently selected from    -   a) halo, formyl, cyano, amino, nitro, thiocyanato,        isothiocyanato, trimethylsilyl, and hydroxy;    -   b) C₁-C₄ alkyl, alkenyl, alkynyl, C₃-C₆ cycloalkyl, and        cycloalkenyl, each optionally substituted with halo, hydroxy,        thio, amino, nitro, cyano, formyl, phenyl, C₁-C₄ alkoxy,        alkylcarbonyl, alkylthio, alkylamino, dialkylamino,        alkoxycarbonyl, (alkylthio)carbonyl, alkylaminocarbonyl,        dialkylaminocarbonyl, alkylsulfinyl, or alkylsulfonyl;    -   c) phenyl, furyl, thienyl, pyrrolyl, each optionally substituted        with halo, formyl, cyano, amino, nitro, C1-C4 alkyl, alkenyl,        alkynyl, alkoxy, alkylthio, alkylamino, dialkylamino, haloalkyl,        and haloalkenyl;    -   d) C1-C4 alkoxy, alkenoxy, alkynoxy, C₃-C₆ cycloalkyloxy,        cycloalkenyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylamino, dialkylamino, alkylcarbonylamino, aminocarbonyl,        alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl,        alkylcarbonyloxy, alkoxycarbonyl, (alkylthio)carbonyl,        phenylcarbonylamino, phenylamino, each optionally substituted        with halo;    -   wherein two R groups may be combined to form a fused ring;    -   each R₂ is independently selected from alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl and phenyl, each optionally substituted        with R₄ or halogen; and wherein, when Q is C, R₂ may also be        selected from halo, alkoxy, alkylthio, alkylamino, and        dialkylamino;    -   wherein two R₂ groups may be combined to form a cyclo group with        Q;    -   R₃ is C₁-C₄ alkyl;    -   R₄ is C₁-C₄ alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or        dialkylamino;    -   R₇ is C₁-C₄ alkyl, haloalkyl, or phenyl, optionally substituted        with halo, nitro, or R₄;    -   or an agronomic salt thereof, and    -   a structure which controls the release of said compound.

The present invention is also directed to a novel microcapsulecomprising a polyurea shell enclosing a core which comprisessilthiopham, where the microcapsule has an average size of from about 2μto about 8μ, where the weight ratio of the shell to the core is fromabout 15:100 to about 30:100, and where the amount of silthiopham in thecore is from about 30% to about 60%, by weight.

The present invention is also directed to a novel method of producing amicroencapsulated form of a high melting material which method is freeof the use of solvents, the method comprising mixing a high meltingmaterial and a melting point depressant to form a composition which isfree of solvents; heating the composition to a temperature at which thecomposition is a liquid, but which temperature is below the normalmelting points of both the high melting material and the melting pointdepressant; forming the liquid composition into small droplets whilemaintaining said liquid composition at a temperature below the normalmelting points of both the high melting material and the melting pointdepressant; and enclosing each droplet in a non-water soluble shell byinterfacial polymerization to form a microcapsule.

Among the several advantages found to be achieved by the presentinvention, therefore, may be noted the provision of a method for theformation of microcapsules enclosing high-melting agricultural activeswhere the method was free of the use of aromatic solvents and where themethod could be carried out at a temperature that was below the normalmelting point of the active, and the provision of a method that allowedfor the use of a polyurea shell that could be designed to release theactive from the microcapsule at a controlled rate when the microcapsulewas exposed to natural environmental conditions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a release rate profile showing the release of silthiopham as afunction of time and as a function of shell wall thickness formicrocapsules of the present invention having 40% silthiopham in thecore, where profiles are shown for microcapsules having shell:coreweight ratios of 15:100, 20:100, and 30:100;

FIG. 2 shows a release rate profile showing the release of silthiophamas a function of time and as a function of shell wall thickness formicrocapsules having 50% silthiopham in the core, where profiles areshown for microcapsules having shell:core weight ratios of 15:100,20:100, and 30:100;

FIG. 3 shows a release rate profile showing the release of silthiophamas a function of time and as a function of shell wall thickness formicrocapsules having 60% silthiopham in the core, where profiles areshown for microcapsules having shell:core weight ratios of 15:100,20:100, and 30:100;

FIG. 4 shows release rate profiles for the release of silthiopham frommicrocapsules having a shell:core ratio of 30:100, where releaseprofiles are shown as a function of the amount of silthiopham originallyin the core;

FIG. 5 shows release rate profiles for the release of silthiopham frommicrocapsules having a shell:core ratio of 15:100, where releaseprofiles are shown as a function of the amount of silthiopham originallyin the core;

FIG. 6 shows release rate profiles for the release of silthiopham frommicrocapsules having a shell:core ratio of 20:100, where releaseprofiles are shown as a function of the amount of silthiopham originallyin the core;

FIG. 7 illustrates the effect of particle size on the release profilesfor the release of silthiopham from microcapsules having a shell:coreratio of 30:100, for microcapsules having an average size of 2.4μ and4.2μ;

FIG. 8 illustrates the effect of particle size on the release profilesfor the release of silthiopham from microcapsules having a shell:coreratio of 20:100 and having a 32% by weight loading of silthiopham in thecore, for microcapsules having an average size of 2.1μ and 4.1μ;

FIG. 9 illustrates the effect on silthiopham release rate of the ratioof triethylene tetramine (TETA)-to-Jeffamine T-403 (T-403, atri-functional amine) that was used in the interfacial polymerization toform a polyurea shell for microcapsules having a shell:core weight ratioof 20:100, and shows the release profiles for the release of silthiophamfor microcapsules produced with TETA/T-403 ratios ranging from 0/100 to100/0;

FIG. 10 illustrates the effect on silthiopham release rate of the ratioof triethylene tetramine (TETA)-to-Jeffamine T-403 (T-403, atri-functional amine) that was used in the interfacial polymerization toform a polyurea shell for microcapsules having a shell:core weight ratioof 30:100, and shows the release profiles for the release of silthiophamfor microcapsules produced with TETA/T-403 ratios of 10/90 and 50/50;

FIG. 11 is a scanning electron micrograph taken at 2000× ofmicrocapsules of the present invention having a 50% by weight loading ofsilthiopham in the core and having a shell:core ratio of 30:100; a 5μscale-bar illustrates the relative size of the microcapsules;

FIG. 12 is a scanning electron micrograph taken at 2000× ofmicrocapsules of the present invention having a 32% by weight loading ofsilthiopham in the core and having a shell:core ratio of 30:100; a 5μscale-bar illustrates the relative size of the microcapsules;

FIG. 13 is a plot of the melting point of a blend of silthiopham andtebuconazole as a function of the relative amounts of each of thecomponents in the blend, and shows that the mixture forms a eutectichaving a melting point approximately 26° C. lower than that ofsilthiopham at a ratio of about 50:50 by weight;

FIG. 14 is a plot of the melting point of a blend of silthiopham andsimeconazole as a function of the relative amounts of each of thecomponents in the blend, and shows that the mixture forms a eutectichaving a melting point approximately 18° C. lower than that ofsilthiopham at a ratio of about 80:20 silthiopham:simeconazole byweight; and

FIG. 15 is a plot of the melting point of a blend of silthiopham andfluorophenyltriazoleethanone as a function of the relative amounts ofeach of the components in the blend, and shows that the mixture forms aeutectic having a melting point approximately 6° C. lower than that ofsilthiopham at a ratio of about 80:20silthiopham:fluorophenyltriazoleethanone by weight.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In accordance with the present invention, it has been discovered thatmicrocapsules containing a high-melting agricultural active material (asthose terms are defined below) can be produced without raising thetemperature of the active to its normal melting point and without theuse of an aromatic solvent. The microcapsules can have an outer shellthat is formed of polyurea and the microcapsules can be designed torelease the active from the microcapsule at a pre-selected controlledrate when the microcapsule is exposed to natural environmentalconditions.

In one embodiment, this disclosure describes the microencapsulation of afirst agricultural active, such as silthiopham, in a polyurea shell,where the encapsulation is achieved by an interfacial polymerizationprocess. Two processes are disclosed for preparing the emulsionnecessary for the interfacial polymerization, one involves encapsulationof the active in solution in a non-aromatic organic solvent and theother involves encapsulation of a blend of the active and a meltingpoint depressant.

The embodiment of the present invention involving the production ofmicrocapsules that contain silthiopham in the core and which are free ofnon-aromatic solvents, is believed to be particularly advantageous. Itis believed that such microcapsules, applied to wheat seed in the fall,could provide an initial level of protection sufficient to protect theseed from harmful biological activity until temperatures fall low enoughthat biological pressure becomes insignificant for the winter, but wouldretain a sufficient amount of the active so that it would still bereleasing at a sufficient level in the spring to provide protectionagainst the increasing biological pressure throughout sprouting andinitial growth of the plant. This type of protection from only one seedtreatment with the novel microcapsules would provide protection for theseeds and the plants and would save at least one, and perhaps two,conventional field applications of a pesticide.

As will be discussed in detail below, it has been found that the novelmicrocapsules can be designed to provide a pre-selected controlled rateof release of an enclosed active, by controlling, among otherparameters, the active loading in the core, the thickness of the shellwall, the particle size, and the composition of the shell wall. Thisability to control the release profile permits the tailoring of themicrocapsules to meet a wide range of application demands. As would beunderstood by one having skill in the art, the release rate of theencapsulated active material would be affected by such environmentalparameters as temperature and moisture. However, one can use thecontrollable parameters described above to provide a desired releaserate for any particular set of environmental conditions. For example, ifone knew the geographic location in which the novel material was to beused, it would be possible to predict the temperature to be expectedduring the different seasons, and to design a material that wouldprovide a certain release rate at the predicted temperatures.

One embodiment of the present invention advantageously extends the stateof the art to include the encapsulation of almost any high melting solidby a method that includes interfacial polymerization, but without thenecessity of using a solvent to dissolve the high melting solid. In U.S.Pat. No. 5,310,721, to Lo, it is taught that microcapsules prepared byinterfacial polycondensation can advantageously contain materials whichhave a variety of uses, such as for dyes, inks, color formers,pharmaceuticals, cosmetics, flavoring materials, agricultural chemicals,and the like. The Lo patent states that any liquid, oil, low meltingsolid, or solvent-soluble material into which a first wall-formingmaterial can be dissolved and which is non-reactive with saidwall-forming material may be encapsulated with this technique.

The present invention extends the state of the art to include theencapsulation of almost any high melting solid by forming a mixture ofthe high melting solid with a melting point depressant that is a solidat conventional interfacial polymerization temperatures (for polyureaformation, this is about 50° C.-90° C.), but is capable of combiningwith the high melting solid to form a eutectic mixture, where themelting point of the eutectic mixture is sufficiently low to permit themixture to be encapsulated by known interfacial polymerizationtechniques, such as referred to in the Lo patent. It is preferable, butnot required, that the melting point depressant is a material of thesame type as the high melting solid. For example, it is particularlyadvantageous when both are dyes, inks, pharmaceuticals, flavoringmaterials, agricultural chemicals, and the like.

As used herein, a “material having a high normal melting point”, whichis also referred to herein as a “high melting material”, is a materialwhich has a normal melting point temperature that is higher than theupper limit of the temperature range that is conventionally used tocarry out the interfacial polymerization method that is being used toform the encapsulating shell around the material. For example, when theinterfacial polymerization method comprises the formation of a polyureashell, the preferred temperature range that is conventionally used isabout 50° C. to about 90° C., more preferably, about 50° C. to about 80°C., even more preferably, about 50° C. to about 70° C., and yet morepreferably, about 50° C. to about 60° C. Therefore, a high meltingmaterial, in this instance, is one having a normal melting point that isabove 90° C., or above the upper limit of another of the preferredranges.

It is preferred that the first agricultural active, the high meltingmaterial, and the melting point depressant, are materials that have alow water solubility. When it is said that such a material has a “lowwater solubility”, or is “non-water soluble”, it is meant that suchmaterial has a solubility in water at 25° C. of less than about 1%, byweight. It is preferred that the water solubility is less than about0.1%, by weight, more preferred that it is less than about 0.01% byweight, yet more preferred that it is less than about 0.001% by weight,and even more preferred that it is less than about 0.0001% by weight.

When the material having a high normal melting point is an agriculturalactive, the terms “high-melting point agricultural active”, or“high-melting active”, as used herein, mean an agricultural activehaving a normal melting point that is the same as described above for ahigh melting material. In general, a high-melting agricultural activematerials is one that is difficult to encapsulate neat by conventionalmethods for forming a polyurea shell around a core of the active.

The “normal melting point” of a material, as those terms are usedherein, refers to the temperature at which the solid form of thematerial is in equilibrium with the liquid form at atmospheric pressure.It is understood that such terms include the description ofmaterials—such as some polymers—which sometimes have a range oftemperature over which melting occurs. In these cases, the normalmelting point of a polymer can be understood to be any temperaturewithin the normal melting range for the polymer; commonly it is atemperature at or near the mid-point of the melting range. For example,a material having a normal melting range of 86° C.-88° C., could be saidto have a normal melting point of about 87° C.

Agricultural active materials that are suitable for use in the presentinvention include the compounds described in U.S. Pat. Nos. 5,482,974,5,486,621, 5,498,630, 5,693,667, 5,693,667, 5,705,513, 5,811,411,5,834,447, 5,849,723, 5,994,270, 5,998,466, 6,028,101, and inpublications WO 93/07751, and EP 0 538 231 A1. In particular, suchcompounds are described in U.S. Pat. No. 5,693,667 and in EuropeanPatent Application No. 0 538 231 A1, which describe compounds having theformula

-   -   wherein Z₁ and Z₂ are C or N and are part of an aromatic ring        selected from benzene, pyridine, thiophene, furan, pyrrole,        pyrazole, thiazole, and isothiazole;    -   A is selected from —C(X)-amine, —C(O)—SR₃, —NH—C(X)R₄, and    -   —C(═NR₃)—XR₇;    -   B is —W_(m)-Q(R₂)₃ or selected from o-tolyl, 1-naphthyl,        2-naphthyl, and 9-phenanthryl, each optionally substituted with        halogen or R₄;    -   Q is C, Si, Ge, or Sn;    -   W is —C(R₃)_(p)H_((2-p))—; or when Q is C, W is selected from        —C(R₃)_(p) H_((2-p))—, —N(R₃)_(m)H_((1-m))—, —S(O)_(p)—, and        —O—;    -   X is O or S;    -   n is 0, 1, 2, or 3;    -   m is 0 or 1;    -   p is 0, 1, or 2;    -   each R is independently selected from    -   a) halo, formyl, cyano, amino, nitro, thiocyanato,        isothiocyanato, trimethylsilyl, and hydroxy;    -   b) C₁-C₄ alkyl, alkenyl, alkynyl, C₃-C₆ cycloalkyl, and        cycloalkenyl, each optionally substituted with halo, hydroxy,        thio, amino, nitro, cyano, formyl, phenyl, C₁-C₄ alkoxy,        alkylcarbonyl, alkylthio, alkylamino, dialkylamino,        alkoxycarbonyl, (alkylthio)carbonyl, alkylaminocarbonyl,        dialkylaminocarbonyl, alkylsulfinyl, or alkylsulfonyl;    -   c) phenyl, furyl, thienyl, pyrrolyl, each optionally substituted        with halo, formyl, cyano, amino, nitro, C₁-C₄ alkyl, alkenyl,        alkynyl, alkoxy, alkylthio, alkylamino, dialkylamino, haloalkyl,        and haloalkenyl;    -   d) C₁-C₄ alkoxy, alkenoxy, alkynoxy, C₃-C₆ cycloalkyloxy,        cycloalkenyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylamino, dialkylamino, alkylcarbonylamino, aminocarbonyl,        alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl,        alkylcarbonyloxy, alkoxycarbonyl, (alkylthio)carbonyl,        phenylcarbonylamino, phenylamino, each optionally substituted        with halo;    -   wherein two R groups may be combined to form a fused ring;    -   each R₂ is independently selected from alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl and phenyl, each optionally substituted        with R₄ or halogen; and wherein, when Q is C, R₂ may also be        selected from halo, alkoxy, alkylthio, alkylamino, and        dialkylamino;    -   wherein two R₂ groups may be combined to form a cyclo group with        Q;    -   R₃ is C₁-C₄ alkyl;    -   R₄ is C₁-C₄ alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or        dialkylamino;    -   R₇ is C₁-C₄ alkyl, haloalkyl, or phenyl, optionally substituted        with halo, nitro, or R₄;    -   or an agronomic salt thereof.

The term “amine” in —C(X)-amine means an unsubstituted, monosubstituted,or disubstituted amino radical, including nitrogen-bearing heterocycles.Examples of substituents for the amino radical include, but are notlimited to, hydroxy; alkyl, alkenyl, and alkynyl, which may be straightor branched chain or cyclic; alkoxyalkyl; haloalkyl; hydroxyalkyl;alkylthio; alkylthioalkyl; alkylcarbonyl; alkoxycarbonyl; aminocarbonyl;alkylaminocarbonyl; cyanoalkyl; mono- or dialkylamino; phenyl,phenylalkyl or phenylalkenyl, each optionally substituted with one ormore C₁-C₆ alkyl, alkoxy, haloalkyl, C₃-C₆ cycloalkyl, halo, or nitrogroups; C₁-C₄ alkyl or alkenyl groups substituted with heterocycles,optionally substituted with one or more C₁-C₄ alkyl, alkoxy, haloalkyl,halo, or nitro groups. Examples of such nitrogen-bearing heterocycles,which are bonded at a nitrogen to —C(X)—, include, but are not limitedto, morpholine, piperazine, piperidine, pyrrole, pyrrolidine, imidazole,and triazoles, each of which may be optionally substituted with one ormore C₁-C₆ alkyl groups.

Specific examples of the amino radicals useful in the present inventioninclude, but are not limited to, ethylamino, methylamino, propylamino,2-methylethylamino, 1-propenylamino, 2-propenylamino,2-methyl-2-propenylamino, 2-propynylamino, butylamino,1,1-dimethyl-2-propynylamino, diethylamino, dimethylamino,N-(methyl)ethylamino, N-(methyl)-1,1(dimethyl)ethylamino, dipropylamino,octylamino, N-(ethyl)-1-methylethylamino, 2-hydroxyethylamino,1-methylpropylamino, chloromethylamino, 2-chloroethylamino,2-bromoethylamino, 3-chloropropylamino, 2,2,2-trifluoroethylamino,cyanomethyl, methylthiomethylamino, (methylsulfonyl)oxyethylamino,2-ethoxyethylamino, 2-methoxyethylamino, N-(ethyl)-2-ethoxyethylamino,1-methoxy-2,2-dimethylpropylamino, cyclopropylamino, cyclobutylamino,cyclopentylamino, cyclohexylamino, methoxymethylamino,N-(methoxymethyl)ethylamino, N-(1-methylethyl)propylamino,1-methylheptylamino, N-(ethyl)-1-methylheptylamino,6,6-dimethyl-2-hepten-4-ynylamino, 1,1-dimethyl-2-propynylamino. Furtherexamples include benzylamino, ethylbenzylamino, 3-methoxybenzylamino,3-(trifluoromethyl)benzylamino, N-methyl-3-(trifluoromethyl)benzylamino,3,4,5-trimethoxybenzylamino, 1,3-benzodioxol-5-ylmethylamino,phenylamino, 3-(1-methylethyl)phenylamino, ethoxyphenylamino,cyclopentylphenylamino, methoxyphenylamino, nitrophenylamino,1-phenylethylamino, N-(methyl)-3-phenyl-2-propenylamino,benzotriazolylphenylmethyl, 2-pyridinylmethylamino,N-(ethyl)-2-pyridinylmethylamino, 2-thienylmethylamino, andfurylmethylamino. Further examples of amino radicals includemethylhydrazino, dimethylhydrazino, N-ethylanilino, and 2-methylanilino.The amine may also be substituted with diethyl N-ethylphosphoramidicacid, t-butoxycarbonyl, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, etc. Of these examples of the amino radical, ethylaminois preferred.

Examples of B include, but are not limited to, trimethylsilyl,ethyldimethylsilyl, diethylmethylsilyl, triethylsilyl,dimethylpropylsilyl, dipropylmethylsilyl, dimethyl-1-(methyl)ethylsilyl,tripropylsilyl, butyldimethylsilyl, pentyidimethylsilyl,hexyldimethylsilyl, cyclopropyldimethylsilyl, cyclobutyldimethylsilyl,cyclopentyldimethylsilyl, cyclohexyldimethylsilyl, dimethylethenylsilyl,dimethylpropenylsilyl, chloromethyldimethylsilyl,2-chloroethyldimethylsilyl, bromomethyldimethylsilyl,bicycloheptyldimethylsilyl, dimethylphenylsilyl,dimethyl-2-(methyl)phenylsilyl, dimethyl-2-fluorophenylsilyl, and othersuch silyl groups of the formula Si(R₂)₃; any such silyl group connectedto the Z₁-Z₂ ring by a methylene group; and any of these groups whereingermanium or tin is substituted for silicon. Of these examples of B,trimethylsilyl is preferred.

Further examples of B include 1,1-dimethylethyl, 1,1-dimethylpropyl,1,1-dimethylbutyl, 1,1-dimethylpentyl, 1-ethyl-1-methylbutyl,2,2-dimethylpropyl, 2,2-dimethylbutyl, 1-methyl-1-ethylpropyl,1,1-diethylpropyl, 1,1,2-trimethylpropyl, 1,1,2-trimethylbutyl,1,1,2,2-tetramethylpropyl, 1,1-dimethyl-2-propenyl,1,1,2-trimethyl-2-propenyl, 1,1-dimethyl-2-butenyl,1,1-dimethyl-2-propynyl, 1,1-dimethyl-2-butynyl,1-cyclopropyl-1-methylethyl, 1-cyclobutyl-1-methylethyl,1-cyclopentyl-1-methylethyl, 1-(1-cyclopentenyl)-1-methylethyl,1-cyclohexyl-1-methylethyl, 1-(1-cyclohexenyl)-1-methylethyl,1-methyl-1-phenylethyl, 1,1-dimethyl-2-chloroethyl,1,1-dimethyl-3-chloropropyl, 1,1-dimethyl-2-methoxyethyl,1,1-dimethyl-2-(methylamino)ethyl, 1,1-dimethyl-2-(dimethylamino)ethyl,1,1-dimethyl-3-chloro-2-propenyl, 1-methyl-1-methoxyethyl,1-methyl-1-(methylthio)ethyl, 1-methyl-1-(methylamino)ethyl,1-methyl-1-(dimethylamino)ethyl, 1-chloro-1-methylethyl,1-bromo-1-methylethyl, and 1-iodo-1-methylethyl. Of these examples of B,1,1-dimethylethyl is preferred.

Further examples of B are 1,1-dimethylethylamino,1,1-dimethylpropylamino, 1,1-dimethylbutylamino,1,1-dimethylpentylamino, 1-ethyl-1-methylbutylamino,2,2-dimethylpropylamino, 2,2-dimethylbutylamino,1-methyl-1-ethylpropylamino, 1,1-diethylpropylamino,1,1,2-trimethylpropylamino, 1,1,2-trimethylbutylamino,1,1,2,2-tetramethylpropylamino, 1,1-dimethyl-2-propenylamino,1,1,2-trimethyl-2-propenylamino, 1,1-dimethyl-2-butenylamino,1,1-dimethyl-2-propynylamino, 1,1-dimethyl-2-butynylamino,1-cyclopropyl-1-methylethylamino, 1-cyclobutyl-1-methylethylamino,1-cyclopentyl-1-methylethylamino,1-(1-cyclopentenyl)-1-methylethylamino, 1-cyclohexyl-1-methylethylamino,1-(1-cyclohexenyl)-1-methylethylamino, 1-methyl-1phenylethylamino,1,1-dimethyl-2-chloroethylamino, 1,1-dimethyl-3-chloropropylamino,1,1-dimethyl-2-methoxyethylamino,1,1-dimethyl-2-(methylamino)ethylamino,1,1-dimethyl-2-(dimethylamino)ethylamino, and1,1-dimethyl-3-chloro-2-propenylamino. Any of these groups may also havea methyl substitution on the nitrogen, as inN-(methyl)-1,1-dimethylethylamino andN-(methyl)-1,1-dimethylpropylamino. Of these examples of B,1,1-dimethylethylamino and N-(methyl)-1,1-dimethylethylamino arepreferred.

Further examples of B include 1,1-dimethylethoxy, 1,1-dimethylpropoxy,1,1-dimethylbutoxy, 1,1-dimethylpentoxy, 1-ethyl-1-methylbutoxy,2,2-dimethylpropoxy, 2,2-dimethylbutoxy, 1-methyl-1-ethylpropoxy,1,1-diethylpropoxy, 1,1,2-trimethylpropoxy, 1,1,2-trimethylbutoxy,1,1,2,2-tetramethylpropoxy, 1,1-dimethyl-2-propenoxy,1,1,2-trimethyl-2-propenoxy, 1,1-dimethyl-2-butenoxy,1,1-dimethyl-2-propynyloxy, 1,1-dimethyl-2-butynyloxy,1-cyclopropyl-1-methylethoxy, 1-cyclobutyl-1-methylethoxy,1-cyclopentyl-1-methylethoxy, 1-(1-cyclopentenyl)-1-methylethoxy,1-cyclohexyl-1-methylethoxy, 1-(1-cyclohexenyl)-1-methylethoxy,1-methyl-1-phenylethoxy, 1,1-dimethyl-2-chloroethoxy,1,1-dimethyl-3-chloropropoxy, 1,1-dimethyl-2-methoxyethoxy,1,1-dimethyl-2-(methylamino)ethoxy,1,1-dimethyl-2-(dimethylamino)ethoxy, 1,1-dimethyl-3-chloro-2-propenoxy.Of these examples of B, 1,1-dimethylethoxy is preferred.

Further examples of B include 1 methylcyclopropyl, 1-methylcyclobutyl,1-methylcyclopentyl, 1-methylcyclohexyl, 1-methylcyclopropylamino,1-methylcyclobutylamino, 1-methylcyclopentylamino,1-methylcyclohexylamino, N-(methyl)-1-methylcyclopropylamino,N-(methyl)-1-methylcyclobutylamino, N-(methyl)-1-methylcyclopentylamino,and N-(methyl)-1-methylcyclohexylamino.

R_(n) may be any substituent(s) which do(es) not unduly reduce theeffectiveness of the compounds to function in the method of diseasecontrol. R_(n) is generally a small group; “n” is preferably 1 forbenzene rings and 2 for furan and thiophene. R is more preferably methylor halogen, and more preferably is located adjacent to A.

When Z₁ and Z₂ are part of a benzene ring, the following are notincluded as useful active agents of the present invention: 1) n is notzero when B is trimethylsilyl and A is N,N-diethylaminocarbonyl,N,N-bis(1-methylethyl)aminocarbonyl, N-methylaminothiocarbonyl,N-ethylaminocarbonyl, 1-piperidinylcarbonyl, or N-phenylaminocarbonyl;or when B is orthotolyl and A is N,N-diethylaminocarbonyl, N,N-bis(1methylethyl)aminocarbonyl, N-methylaminocarbonyl, or O-methylcarbamyl;or when B is 1,1-dimethylethyl and A is N,N-dimethylaminothiocarbonyl orN-phenylaminocarbonyl; or when B is trimethylstannyl and A isN,N-diethylaminocarbonyl or O-(1,1-dimethylethyl)carbamyl; 2) when B is2-trimethylsilyl and A is N,N-diethylaminocarbonyl, R_(n) is not3-fluoro-6-formyl, 3-fluoro-6methyl, 3-chloro-6-formyl, 3-fluoro,3-chloro, 3-chloro-6-methyl, 6-trimethylsilyl, or 6-methyl; 3) when A isO-(1,1-dimethylethyl)carbamyl and B is 2-trimethylsilyl, R_(n) is not5-trifluoromethyl; 4) when A is N-phenylaminocarbonyl and B is2,2-dimethylpropyl, R_(n) is not 3-methyl; and 5) R is notisothiocyanato when A is —C(O)-amine and W_(m) is —O—.

When Z₁ and Z₂ are part of a thiophene, furan or pyrrole ring, the novelcompounds of the present invention do not include B equal totrimethylsilyl when A is (diethylamino)carbonyl.

Useful agricultural actives of the type described above have also beendescribed in U.S. Pat. No. 5,998,466 as a compound having the formula

-   -   wherein Z₁ and Z₂ are C or N and are part of an aromatic ring        which is thiophene;    -   A is selected from —C(X)-amine, wherein the amine is substituted        with a first and a second amine substituent or with an        alkylaminocarbonyl and a hydrogen, —C(O)—SR₃, —NH—C(X)R₄, and        —C(═NR₃)—XR₇;    -   the first amine substituent which is selected from the group        consisting of C₁-C₁₀ straight or branched alkyl, alkenyl, or        alkylaryl groups or mixtures thereof optionally substituted with        one or more halogen, hydroxy, alkoxy, alkylthio, nitrile,        alkylsulfonate, haloalkylsulfonate, phenyl, C₃-C₆ cyclocalkyl        and C₅-C₆ cycloalkynel; phenyl optionally substituted with one        or more C₁-C₄ straight or branched alkyl, alkenyl, or alkynyl        groups or mixtures thereof, cycloalkyl, cycloalkenyl, haloalkyl,        alkoxy and nitro; C₃-C₆ cycloalkyl, C₅-C₆ cycloalkenyl, alkoxy,        alkenoxy, alkynoxy, dialkylamino, and alkylthio;    -   and the second amine substituent which is selected from the        group consisting of hydrogen; C₁-C₆ straight or branched alkyl,        alkenyl, or alkynyl groups or mixtures thereof optionally        substituted with one or more halogen; hydroxy, alkylcarbonyl,        haloalkylcarbonyl, alkoxycarbonyl, and dialkylcarbonyl;    -   B is —W_(m)-Q(R₂)₃ or selected from o-tolyl, 1-naphthyl,        2-naphthyl, and 9-phenanthryl, each optionally substituted with        halogen or R₄;    -   Q is C, Si, Ge, or Sn;    -   W is —C(R₃)_(p)H_((2-p))—; or when Q is C, W is selected from        —C(R₃)_(p)H_((2-p))—, —N(R₃)_(m)H_((1-m))—, —S(O)_(p)—, and —O—;    -   X is O or S;    -   n is 2;    -   m is 0 or 1;    -   p is 0, 1, or 2;    -   wherein two R groups are combined to form a nonheterocyclic ring        fused with the thiophene ring, which is not a benzothiophene        other than a tetrahydrobenzothiophene, said two R groups being        selected from the group consisting of C₁-C₄ alkyl, alkenyl,        C₃-C₆ cycloalkyl and cycloalkenyl, each optionally substituted        with hydroxy, thio, phenyl, C₁-C₄ alkoxy, alkylthio,        alkylsulfinyl, or alkylsulfonyl;    -   each R₂ is independently selected from alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl and phenyl, each optionally substituted        with R₄ or halogen; and wherein, when Q is C, R₂ may also be        selected from halo, alkoxy, alkylthio, alkylamino, and        dialkylamino; and further when Q is C, then two R₂ groups may be        combined to form a cycloalkyl group with Q;    -   R₃ is C₁-C₄ alkyl;    -   R₄ is C₁-C₄ alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or        dialkylamino; and    -   R₇ is C₁-C₄ alkyl, haloalkyl, or phenyl optionally substituted        with halo, nitro, or R₄;    -   or an agronomic salt thereof.

The terms “amine”, “alkyl”, “alkoxy”, “alkoxyalkyl”, “monoalkylamino”,“dialkylamino”, “haloalkyl”, and “halo”, and B, R_(n), and the featuresof Z₁ and Z₂, are as described above.

Agricultural actives that are useful in the present invention can alsobe selected from those described in U.S. Pat. No. 5,482,974, namely, acompound having the formula

-   -   wherein R² is ethyl, iso-propyl, propyl or allyl;    -   A is N(CH₃)_(1-n)H_(n)R⁵ or OR⁶ wherein n is 0 or 1, R⁵ is        (CH₃)_(m)(CH₃CH₂)_(3-m)C, 1-methyl-1-cyclopentyl,        1-methyl-1-cyclohexyl or 2,3-dimethyl-2-butyl wherein m is 0, 1,        2 or 3 and R⁶ is independently R⁵, or 2,3,3-trimethyl-2-butyl;    -   R³ is H or independently R⁴; and    -   R⁴ is halo or CH₃;    -   with the proviso that when A is N(CH₃)_(1-n)H_(n)R⁵, if R³ is H        and R⁵ is 1-methyl-1-cyclohexyl or (CH₃)_(m)(CH₂ CH₃)_(3-m)C,        where m is 0 or 3, or if R³ is halo and R² is        (CH₃)_(m)(CH₃CH₂)_(3-m)C, where m is 3, then R² cannot be ethyl;    -   and with the proviso that when A is OR⁶ then m is equal to or        less than 2, and if R³ is H or halo and R² is ethyl or        isopropyl, then R⁶ is (CH₃)_(M)(CH₃CH₂)_(3-M)C where m is 1; or        an agronomic salt thereof.

Active agents that are useful in the present invention can also beselected from those described in U.S. Pat. No. 5,994,270, namely, acompound having the formula

-   -   where A is —C(X)-amine; B is —W_(m)-Q(R₂)₃; and A can be B when        B is A except when the formula is f), then Q cannot be Si;    -   Q is C or Si;    -   W is —NH—, —O— or NCH₃—;    -   X is O or S;    -   m is 0 or 1, provided that m is 0 when Q is Si;    -   n is 0, 1, 2, or 3    -   p is 0, 1 or 2, and n plus p is equal to or less than 3; each R        is independently selected from    -   a) halo, formyl, cyano, amino, nitro, thiocyanato,        isothiocyanato, trimethylsilyl, and hydroxy;    -   b) C₁-C₄ alkyl, alkenyl, alkynyl, C₃-C₆ cycloalkyl, and        cycloalkenyl, each optionally substituted with halo, hydroxy,        thio, amino, nitro, cyano, formyl, phenyl, C₁-C₄ alkoxy,        alkylcarbonyl, alkylthio, alkylamino, dialkylamino,        alkoxycarbonyl, (alkylthio)carbonyl, alkylaminocarbonyl,        dialkylaminocarbonyl, alkylsulfinyl, or alkylsulfonyl;    -   c) phenyl, furyl, thienyl, pyrrolyl, each optionally substituted        with halo, formyl, cyano, amino, nitro, C₁-C₄ alkyl, alkenyl,        alkynyl, alkoxy, alkylthio, alkylamino, dialkylamino, haloalkyl,        and haloalkenyl;    -   d) C₁-C₄ alkoxy, alkenoxy, alkynoxy, C₃-C₆ cycloalkyloxy,        cycloalkenyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylamino, dialkylamino, alkylcarbonylamino, aminocarbonyl,        alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl,        alkylcarbonyloxy, alkoxycarbonyl, (alkylthio)carbonyl,        phenylcarbonylamino, phenylamino, each optionally substituted        with halo; each R₂ is independently selected from alkyl,        alkenyl, alkynyl, cycloalkyl, cycloalkenyl and phenyl, each        optionally substituted with R₄ or halogen; and wherein, when Q        is C, R₂ may also be selected from halo, alkoxy, alkylthio,        alkylamino, and dialkylamino; wherein two R₂ groups may be        combined to form a cyclo group with Q; R₄ is C₁-C₄ alkyl,        haloalkyl, alkoxy, alkylthio, alkylamino, or dialkylamino; or an        agronomic salt thereof.

The term “amine” in —C(X)-amine means an unsubstituted, monosubstituted,or disubstituted amino radical, including nitrogen-bearing heterocycles.Examples of substituents for the amino radical include, but are notlimited to, hydroxy; alkyl, alkenyl, and alkynyl, which may be straightor branched chain or cyclic; alkoxyalkyl; haloalkyl; hydroxyalkyl;alkylthio; alkylthioalkyl; alkylcarbonyl; alkoxycarbonyl; aminocarbonyl;alkylaminocarbonyl; cyanoalkyl; mono- or dialkylamino; phenyl,phenylalkyl or phenylalkenyl, each optionally substituted with one ormore C₁-C₆ alkyl, alkoxy, haloalkyl, C₃-C₆ cycloalkyl, halo, or nitrogroups; C1-C4 alkyl or alkenyl groups substituted with heterocycles,optionally substituted with one or more C₁-C₄ alkyl, alkoxy, haloalkyl,halo, or nitro groups. Examples of such nitrogen-bearing heterocycles,which are bonded at a nitrogen to —C(X)—, include, but are not limitedto, morpholine, piperazine, piperidine, pyrrole, pyrrolidine, imidazole,and triazoles, each of which may be optionally substituted with one ormore C₁-C₆ alkyl groups.

Specific examples of the amino radicals useful in the present inventioninclude, but are not limited to, ethylamino, methylamino, propylamino,2-methylethylamino, 1-propenylamino, 2-propenylamino,2-methyl-2-propenylamino, 2-propynylamino, butylamino,1,1-dimethyl-2-propynylamino, diethylamino, dimethylamino,N-(methyl)ethylamino, N-(methyl)-1,1-(dimethyl)ethylamino,dipropylamino, octylamino, N-(ethyl)-1-methylethylamino,2-hydroxyethylamino, 1-methylpropylamino, chloromethylamino,2-chloroethylamino, 2-bromoethylamino, 3-chloropropylamino,2,2,2-trifluoroethylamino, cyanomethyl, methylthiomethylamino,(methylsulfonyl)oxyethylamino, 2-ethoxyethylamino, 2-methoxyethylamino,N-(ethyl)-2-ethoxyethylamino, 1-methoxy-2,2-dimethylpropylamino,cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino,methoxymethylamino, N-(methoxymethyl)ethylamino,N-(1-methylethyl)propylamino, 1-methylheptylamino,N-(ethyl)-1-methylheptylamino, 6,6-dimethyl-2-hepten-4-ynylamino,1,1-dimethyl-2-propynylamino. Further examples include benzylamino,ethylbenzylamino, 3-methoxybenzylamino, 3-(trifluoromethyl)benzylamino,N-methyl-3-(trifluoromethyl)benzylamino, 3,4,5-trimethoxybenzylamino,1,3-benzodioxol-5-ylmethylamino, phenylamino,3-(1-methylethyl)phenylamino, ethoxyphenylamino, cyclopentylphenylamino,methoxyphenylamino, nitrophenylamino, 1-phenylethylamino,N-(methyl)-3-phenyl-2-propenylamino, benzotriazolylphenylmethyl,2-pyridinylmethylamino, N-(ethyl)-2-pyridinylmethylamino,2-thienylmethylamino, and furylmethylamino.

Further examples of amino radicals include methylhydrazino,dimethylhydrazino, N-ethylanilino, and 2-methylanilino. The amine mayalso be substituted with diethyl N-ethylphosphoramidic acid,t-butoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.Of these examples of the amino radical, ethylamino, propylamino, orallylamino is preferred.

Examples of B include, but are not limited to, trimethylsilyl,ethyldimethylsilyl, diethylmethylsilyl, triethylsilyl,dimethylpropylsilyl, dipropylmethylsilyl, dimethyl-1-(methyl)ethylsilyl,tripropylsilyl, butyldimethylsilyl, pentyidimethylsilyl,hexyldimethylsilyl, cyclopropyldimethylsilyl, cyclobutyldimethylsilyl,cyclopentyidimethylsilyl, cyclohexyldimethylsilyl, dimethylethenylsilyl,dimethylpropenylsilyl, chloromethyldimethylsilyl,2-chloroethyldimethylsilyl, bromomethyldimethylsilyl,bicycloheptyldimethylsilyl, dimethylphenylsilyl,dimethyl-2-(methyl)phenylsilyl, dimethyl-2-fluorophenylsilyl, and othersuch silyl groups of the formula Si(R₂)₃. Of these examples of B,trimethylsilyl is preferred.

Further examples of B include 1,1-dimethylethyl, 1,1-dimethylpropyl,1,1-dimethylbutyl, 1,1-dimethylpentyl, 1-ethyl-1-methylbutyl,2,2-dimethylpropyl, 2,2-dimethylbutyl, 1-methyl-1-ethylpropyl,1,1-diethylpropyl, 1,1,2-trimethylpropyl, 1,1,2-trimethylbutyl,1,1,2,2-tetramethylpropyl, 1,1-dimethyl-2-propenyl,1,1,2-trimethyl-2-propenyl, 1,1-dimethyl-2-butenyl,1,1-dimethyl-2-propynyl, 1,1-dimethyl-2-butynyl,1-cyclopropyl-1-methylethyl, 1-cyclobutyl-1-methylethyl,1-cyclopentyl-1-methylethyl, 1-(1-cyclopentenyl)-1-methylethyl,1-cyclohexyl-1-methylethyl, 1-(1-cyclohexenyl)-1-methylethyl,1-methyl-1-phenylethyl, 1,1-dimethyl-2-chloroethyl,1,1-dimethyl-3-chloropropyl, 1,1-dimethyl-2-methoxyethyl,1,1-dimethyl-2-(methylamino)ethyl, 1,1-dimethyl-2-(dimethylamino)ethyl,1,1-dimethyl-3-chloro-2-propenyl, 1-methyl-1-methoxyethyl,1-methyl-1-(methylthio)ethyl, 1-methyl-1-(methylamino)ethyl,1-methyl-1-(dimethylamino)ethyl, 1-chloro-1-methylethyl,1-bromo-1-methylethyl, and 1-iodo-1-methylethyl. Of these examples of B,1,1-dimethylpropyl, 1,1-diethylethyl or 1-methyl-1-cyclopentyl ispreferred.

Further examples of B are 1,1-dimethylethylamino,1,1-dimethylpropylamino, 1,1-dimethylbutylamino,1,1-dimethylpentylamino, 1-ethyl-1-methylbutylamino,2,2-dimethylpropylamino, 2,2-dimethylbutylamino,1-methyl-1-ethylpropylamino, 1,1-diethylpropylamino,1,1,2-trimethylpropylamino, 1,1,2-trimethylbutylamino,1,1,2,2-tetramethylpropylamino, 1,1-dimethyl-2-propenylamino,1,1,2-trimethyl-2-propenylamino, 1,1-dimethyl-2-butenylamino,1,1-dimethyl-2-propynylamino, 1,1-dimethyl-2-butynylamino,1-cyclopropyl-1-methylethylamino, 1-cyclobutyl-1-methylethylamino,1-cyclopentyl-1-methylethylamino,1-(1-cyclopentenyl)-1-methylethylamino, 1-cyclohexyl-1-methylethylamino,1-(1-cyclohexenyl)-1-methylethylamino, 1-methyl-1-phenylethylamino,1,1-dimethyl-2-chloroethylamino, 1,1-dimethyl-3-chloropropylamino,1,1-dimethyl-2-methoxyethylamino,1,1-dimethyl-2-(methylamino)-ethylamino,1,1-dimethyl-2-(dimethylamino)ethylamino, and1,1-dimethyl-3-chloro-2-propenylamino. Of these examples of B,1,1-dimethylpropylamino, 1,1-ethylethylamino or1-methyl-1-cyclopentylamino is preferred.

Further examples of B include 1,1-dimethylethoxy, 1,1-dimethylpropoxy,1,1-dimethylbutoxy, 1,1-dimethylpentoxy, 1-ethyl-1-methylbutoxy,2,2-dimethylpropoxy, 2,2-dimethylbutoxy, 1-methyl-1-ethylpropoxy,1,1-diethylpropoxy, 1,1,2-trimethylpropoxy, 1,1,2-trimethylbutoxy,1,1,2,2-tetramethylpropoxy, 1,1-dimethyl-2-propenoxy,1,1,2-trimethyl-2-propenoxy, 1,1-dimethyl-2-butenoxy,1,1-dimethyl-2-propynyloxy, 1,1-dimethyl-2-butynyloxy,1-cyclopropyl-1-methylethoxy, 1-cyclobutyl-1-methylethoxy,1-cyclopentyl-1-methylethoxy, 1-(1-cyclopentenyl)-1-methylethoxy,1-cyclohexyl-1-methylethoxy, 1-(1-cyclohexenyl)-1-methylethoxy,1-methyl-1-phenylethoxy, 1,1-dimethyl-2-chloroethoxy,1,1-dimethyl-3-chloropropoxy, 1,1-dimethyl-2-methoxyethoxy,1,1-dimethyl-2-(methylamino)ethoxy,1,1-dimethyl-2-(dimethylamino)ethoxy, 1,1-dimethyl-3-chloro-2-propenoxy.Of these examples of B, 1,1-dimethylpropyloxy, 1,1-diethylethyloxy orcyclopentyloxy is preferred.

Further examples of B include 1-methylcyclopropyl, 1-methylcyclobutyl,1-methylcyclopentyl, 1-methyl-cyclohexyl, 1-methylcyclopropylamino,1-methyl-cyclobutylamino, 1-methylcyclopentylamino, and1-methyl-cyclohexylamino.

Rn may be any substituent(s) which do(es) not unduly reduce theeffectiveness of the compounds to function in the method of control ofGaeumannomyces graminis var. tritici. R_(n) is generally a small group;“n” is preferably 0 or 1. R is preferably methyl or halogen.

As used to describe the compounds discussed just above, the term“alkyl”, unless otherwise indicated, means an alkyl radical, straight orbranched chain, having, unless otherwise indicated, from 1 to 10 carbonatoms. The terms “alkenyl” and “alkynyl” mean unsaturated radicalshaving from 2 to 7 carbon atoms. Examples of such alkenyl groups includeethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl,2-methyl-1-propenyl, 2-methyl-2-propenyl, 1-methylethenyl, and the like.Examples of such alkynyl groups include ethynyl, 1-propynyl, 2-propynyl,1,1-dimethyl-2-propynyl, and so forth. Substituent groups may also beboth alkenyl and alkynyl, for example, 6,6-dimethyl-2-hepten-4-ynyl.

As used to describe the compounds discussed just above, the term“alkoxy” means an alkyl group having, unless otherwise indicated, from 1to 10 carbon atoms connected via an ether linkage. Examples of suchalkoxy groups include methoxy, ethoxy, propoxy, 1-methylethoxy, and soforth.

As used to describe the compounds discussed just above, the term“alkoxyalkyl” means an ether radical having, unless otherwise indicated,from 1 to 10 carbon atoms. Examples of such alkoxyalkyl groups includemethoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, and so forth.

As used to describe the compounds discussed just above, the terms“monoalkylamino” and “dialkylamino” each mean an amino group having,respectively, 1 or 2 hydrogens replaced with an alkyl group.

As used to describe the compounds discussed just above, the term“haloalkyl” means an alkyl radical having one or more hydrogen atomsreplaced by halogens, including radicals having all hydrogen atomssubstituted by halogen. Examples of such haloalkyl groups arefluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,trichloromethyl, and so forth.

As used to describe the compounds discussed just above, the term “halo”means a radical selected from chloro, bromo, fluoro, and iodo.

A preferred active agent is a compound having the structure

-   -   and which is known as        4,5-dimethyl-N-(2-propenyl)-2-(trimethylsilyl)-3-thiophenecarboxamide,        having a CAS registration number of 175217-20-6, and for which        the proposed ISO common name is “Silthiopham”, or “Sylthiopham”.        In this specification, this active agent may be referred to as        silthiopham.

In this specification, the agricultural actives that are described abovecan be referred to as a “first agricultural active”. In anotherembodiment, the first agricultural active can include simeconazole.

The first agricultural active material of the present invention can beused in any purity that passes for such material in the commercialtrade. The material can be used in any form in which it is received fromthe supplier, or in which it is synthesized. However, if a solvent ispresent, such solvents are non-aromatic organic liquid solvents that areamong those that are described herein below.

When the first agricultural active is mixed with a solvent in order toform an organic phase that is a liquid at temperatures lower than thenormal melting point of the first agricultural active, the solvent canbe a non-aromatic organic liquid in which the active is soluble in aamount of at least about 5%, by weight, at 70° C. Preferably, thesolvent is one in which the active is soluble in an amount of at leastabout 20%, by weight, more preferably at least about 40%, by weight,even more preferably at least about 50%, by weight, and yet morepreferably at least about 60%, by weight, all at a temperature of 70° C.

It is preferred that the solvent has a normal boiling point that ishigher than the upper level of the normal range of temperature that iscommonly used for the polymerization reaction of the encapsulationmethod that is being used. A boiling point of at least about 20° C.above this upper level is preferred, at least about 30° C. above thisupper level is even more preferred, and at least about 50° C. above thisupper level is yet more preferred.

Suitable solvents for the present method can be found in OrganicSolvents Physical Properties and Method of Purification, by Riddick, J.A., W. B. Bunger and T. K. Sakano, John Wiley & Sons, New York (1984)and can be selected from hydrocarbons, hydroxy compounds (but excludingalcohols that react more rapidly with the isocyanates that are used inthe synthesis of the shell material than such isocyanates react with theamines that are used), ethers, carbonyls, acids, esters, halogenatedhydrocarbons, polychlorinated hydrocarbons, brominated hydrocarbons,iodinated hydrocarbons, mixed halogenated hydrocarbons, nitro compounds,amides, sulfides, thioethers, oxo-sulfur compounds, and compounds havingmore than one type of characteristic atom or group. It is preferred thatthe solvent for use in the present method be selected from hydrocarbons,hydroxy compounds, ethers, carbonyls, esters and compounds with morethan one type of characteristic atom or group.

When the solvent is a hydrocarbon, saturated aliphatic hydrocarbons suchas, for example, decane, octane and dodecane, and unsaturatedhydrocarbons (excluding those having an aromatic group) and including,for example, i-dodecane, 2-pinene, camphene, limonene, and the like, areuseful.

Examples of hydroxy compounds that are useful include aliphatic alcoholsthat are not water soluble, such as cyclohexanol, 1-octanol, and thelike.

Examples of ethers that are useful include aliphatic ethers that are notwater soluble, such as dibutyl ether and the like.

Examples of carbonyls include camphor and the like.

Examples of esters include butyl acetate, glyceryl triacetate, butylstearate, hexyl acetate, acetyltri-n-butyl citrate and diethyl adipate,and the like. A preferred solvent is acetyltri-n-butyl citrate (which isavailable under the trade name Citroflex A-4, from Morflex, Inc.,Greensboro, N.C.).

When the liquid composition that contains the first agricultural activeis formed by mixing the active with a solvent, it is preferred that themixture contains at least about 5% by weight of the active, morepreferred is about 25%, and even more preferred is about 50% by weightof the active. It is usually desirable to accommodate as much of theactive ingredient in the core material as possible in order to extendthe useful life of the microcapsules in normal use, however, as will bediscussed below, it is sometimes necessary to provide the active at alevel that is lower than the maximum amount possible in order to obtainthe release rate characteristics that are desired.

When the active material is silthiopham, it is generally preferred tohave from about 5% to about 90% by weight of silthiopham in the core,from about 10% to about 80% by weight is more preferred, from 20% toabout 70% is yet more preferred, and from about 30% to about 60% byweight is even more preferred in order to obtain a desirable combinationof release rate and duration of release.

When the first agricultural active is mixed with a solvent in order toform the liquid composition that will form the core of themicroparticles, other agricultural actives—in addition to the firstactive—can also be added to the mixture. The second, or subsequent,agricultural active can be almost any agricultural active, but ispreferably a pesticide or herbicide. The second active is morepreferably an insecticide, acaracide, bactericide, fungicide, nematocideor molluscicide. When the second active is a fungicide, it is preferablyselected from a group consisting of tebuconazole, tetraconazole,simeconazole, difenoconazole, fluquinconazole, fludioxonil, captan,metalaxyl, carboxin, and thiram.

When the second, or subsequent, agricultural active is a herbicide, itcan be selected from the following useful herbicides:

-   -   growth regulators, including    -   phenoxy acetic acids, such as, 2,4-D and MCPA,    -   phenoxy propionic acids, such as, dichlorprop and mecoprop,    -   phenoxy butyric acids, such as, 2,4-DB and MCPB,    -   benzoic acids, such as, dicamba,    -   picolinic acid and related compounds, such as, picloram,        triclopyr,    -   clopyralid and quinclorac;    -   inhibitors of auxin transport, including    -   naptalam,    -   semicarbones, such as, diflufenzopyr-sodium,    -   s-triazines, such as, atrazine, simazine, cyanazine, prometon,        ametryn and prometryn,    -   other triazines, such as, hexazinone and metribuzin,    -   substituted ureas, such as, diuron, fluometuron, linuron and        tebuthiuron,    -   uracils, such as, bromacil and terbacil,    -   benzothiadiazoles, such as, bentazon,    -   benzonitroles, such as, bromoxymil,    -   phenylcarbamates, such as, desmediphram and phenmedipham,    -   pyridazinones, such as, pyrazon,    -   phenypyriddazines, such as, pyridate, and    -   others, such as, propanil; pigment inhibitors, including    -   amitrole, clomazone and fluridone,    -   pyridazinones, such as, norflurazon,    -   isoxazoles, such as, isoxaflutole;    -   growth inhibitors, including    -   mitotic disruptors, of the types,    -   dinitroanilines, such as, benefin, ethalfluralin, oryzalin,        pendimethalin, prodiamine and trifluralin,    -   oxysulfurons, such as, fluthiamide,    -   pyridines, such as, dithiopyr and thiazopyr,    -   amides, such as, pronamide, and    -   others, such as, DCPA;    -   inhibitors of shoots of emerging seedlings, of the types,    -   carbamothioates, such as, EPTC, cycloate, pebulate, triallate,        butylate, molinate, thiobencarb and bernolate;    -   inhibitors of roots only of seedlings, of the types,    -   amides, such as, napropamide,    -   phenylureas, such as, siduron, and    -   others, such as bensulide, betasan and bensumec;    -   inhibitors of roots and shoots of seedlings, of the types,    -   chloroacetamides, such as, acetochlor, dimetenamid, propachlor,        alachlor and metolachlor;    -   inhibitors of amino acid synthesis, including,    -   inhibitors of aromatic amino acid synthesis, such as, glyphosate        and sulfosate,    -   inhibitors of branched chain amino acid synthesis, of the types,    -   sulfonylureas, such as, bensulfuron, chlorsulfuron,        halosulfuron, nicosulfuron, prosulfuron, fimsulfuron,        thifensulfuron, tribenuron, chlorimuron, ethametsulfuron,        metsulfuron, primisulfuron, oxasulfuron, sulfometuron,        triasulfuron and triflusulfuron,    -   imidazolinones, such as, imazamethabenz, imazamox, imazapic,        imazapyr, imazaquin and imazethapyr,    -   triazolopyrimidines, such as, chloransulam and flumetsulam,    -   tyrimidinyloxybenzoates, such as, pyrithiobac;    -   lipid biosynthesis inhibitors, including,    -   aryoxyphenoxyproprionates, such as, ciclofop-methyl,        fenoxaprop-ethyl, fenoxaprop-p-ethyl, fluazifop-p-butyl,        haloxyfop and quizalofop-p-ethyl,    -   cyclohexanediones, such as, clethodim, sethoxydim and        tralkoxydim;    -   inhibitors of cell wall biosynthesis, including,    -   nitriles, such as, dichlobenil,    -   benzamides, such as, isoxaben, and    -   others, such as, quinclorac;    -   cell membrane disrupters, including,    -   dilute sulfuric acid, monocarbamide dihydrogen sulfate and        herbicidal oils,    -   bipyridyliums, such as, diquat and paraquat,    -   diphenylethers, such as, acifluorfen, fomesafen, lactofen and        oxyfluorfen,    -   oxidiazoles, such as, fluthiacet and oxadiazon,    -   N-phenylheterocycles, such as carfentrazone, flumiclorac and        sulfentrazone;    -   inhibitors of glutamine synthetase, such as glufosinate; and    -   others, such as, DSMA, MSMA, asulam, endothall, ethofumesate,        difenzoquat and TCA.

An alternative method for providing the liquid composition containingthe agricultural active comprises intermixing the first agriculturalactive with a melting point depressant in order to form an organic phasethat is a liquid at temperatures below the normal melting point of theactive. A melting point depressant of the present invention is amaterial that, when intermixed with the first agricultural active, iscapable of forming a eutectic mixture having a melting point that islower than the melting point of both the first agricultural active andthe melting point depressant. It is preferred that the melting pointdepressant is one that has a normal melting point that is above normalambient temperature. As used herein, a “eutectic mixture” is a mixtureof two or more materials having the lowest melting point that isobtainable by varying the proportions of the components.

The inventors have found that, surprisingly, certain agricultural activematerials, other than the first agricultural actives described above,can act as the melting point depressant of the present method. In thisspecification any agricultural active, other than the first agriculturalactives that are described above, can be referred to as a secondagricultural active. When a second agricultural active acts as a meltingpoint depressant, such active can be a pesticide or herbicide, and canbe selected from insecticides, acaricides, bactericides, fungicides,nematocides, molluscicides, and the like.

When a fungicide is used as the melting point depressant, suchfungicides as tebuconazole, simeconazole, fludioxonil, fluquinconazole,difenoconazole,4,5-dimethyl-N-(2-propenyl)-2-(trimethylsilyl)-3-thiophenecarboxamide(sylthiopham), hexaconazole, etaconazole, propiconazole, triticonazole,flutriafol, epoxiconazole, fenbuconazole, bromuconazole, penconazole,imazalil, tetraconazole, flusilazole, metconazole, diniconazole,myclobutanil, triadimenol, bitertanol, pyremethanil, cyprodinil,tridemorph, fenpropimorph, kresoxim-methyl, azoxystrobin, ZEN90160,fenpiclonil, benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, orfurace,oxadixyl, carboxin, prochloraz, trifulmizole, pyrifenox,acibenzolar-5-methyl, chlorothalonil, cymoaxnil, dimethomorph,famoxadone, quinoxyfen, fenpropidine, spiroxamine, triazoxide,BAS50001F, hymexazole, pencycuron, fenamidone, guazatine, andcyproconazole, are suitable for use. Fungicides such as tebuconazole,simeconazole, difenoconazole, tetraconazole, fluquinconazole,fludioxonil, captan, metalaxyl, carboxin and thiram, are preferred.

When a herbicide is used as the melting point depressant, the herbicidecan be selected from the list of herbicides that are described above asbeing appropriate for use as a second or subsequent agricultural active.

In one preferred embodiment of the present method the liquid compositionincludes silthiopham as a first agricultural active and the silthiophamis intermixed with a second agricultural active that results in theformation of a mixture having a melting point that is at least about 5°C. lower than the melting point of silthiopham. It is more preferredthat the melting point of the mixture be at least about 10° C., evenmore preferred at least about 15° C., and yet more preferred that it beat least about 20° C. lower than the melting point of silthiopham.

Tebuconazole and simeconazole have been found to be preferred meltingpoint depressants. A mixture of silthiopham and tebuconazole has beenfound to be a eutectic mixture having a eutectic point at a temperatureof about 60° C., which is significantly lower than the melting point ofeither silthiopham (m.p. about 86° C.-88° C.) or tebuconazole (m.p.about 105° C.). For further information about the physical properties ofpesticides, see, e.g., The Pesticide Manual, 11^(th) Ed., C. D. S.Tomlin, Ed., British Crop Protection Council, Farnham, Surry, UK (1997).

After the liquid composition that contains the agricultural actives isformed by using a non-aromatic solvent, or by using a melting pointdepressant, as described above, the composition is dispersed into smalldroplets. As used herein, the term “small droplets” means dropletshaving an average size of less than about 20μ. Although any method maybe used for dispersing the liquid composition into droplets, a commonlyused method is to mix the organic liquid composition with a sufficientamount of an aqueous liquid to form a continuous phase, and to carry outthe mixing at high rates of shear, such as may be applied by a highshear mixer or blender.

When the small droplets of the liquid composition are formed, it hasbeen found that the size of the droplets is a function of the rate ofshear that is applied to the liquids during mixing, the viscosity of thetwo liquid phases, and the presence, type and amount of a surfactant oremulsifier material.

Surfactant or emulsifier materials that have been found to be useful inthe present method include Lomar D (a sodium salt of naphthalenesulfonic acid polymer, 81% (CAS No. 9084-06-4) sodium sulfate, 12.5%,and water, 6.5%; available from Cognis Corp.) and Sokolan CP 9 (sodiumsalt of maleic acid-olefin copolymer (CAS No. 127123-37-3) availablefrom BASF, Parsippany, N.J.).

A preferred method of forming the shell that encloses the small liquiddroplets is by an interfacial polymerization of monomers to form apolyurea shell around each droplet. A method for accomplishing thispolymerization is to add one or more types of isocyanate monomers to theorganic liquid composition. The organic liquid composition can then bedispersed in the aqueous phase. One or more polyamine monomers can thenbe added to the aqueous liquid in which the organic liquid compositionis dispersed. The polyamines react with the isocyanates at theinterfacial surface of the small droplets (the organic/aqueousinterface) to form a solid polyurea shell that encloses the droplets.

The isocyanates that are useful in the present method includepolyisocyanates that can react with polyamines to form polyurea. One ormore polyisocyanates can be used. Polyisocyanates that are useful in thepresent invention are discussed in Chemistry and Technology ofIsocyanates, Ulrich, H., John Wiley & Sons, New York, (1996).

Monomeric polyisocyanates include aliphatic, cycloaliphatic,araliphatic, aromatic, and heterocyclic polyisocyanates. Examples ofsuch polyisocyanates include 1,12-dodecane diisocyanatecyclobutane-1,3-diisocyanate, cyclohexane-1,3-diisocyanate, 2,4- and/or2,6-hexahydrotoluylene diisocyanate, 4,4′,4″-triphenylmethanetriisocyanate, tris-(4-isocyanatophenyl)-thiophosphate, Desmodur N3300with a CA registration No: 104559-01-5, OCN—R—(O—CH₂CH₂)_(x)—R—NCO(polyethylene glycol), OCN—R—(OCH₂—CH—CH₃)_(x)—R—NCO (polypropyleneglycol), OCN—R—(OCH₂CH₂CH₂CH₂)_(x)—R—NCO (polytetramethylene glycol),OCN—R—(OCH₂CH₂OCO—CH₂CH₂C H₂CH₂—CO)_(x)—R—NCO (polyethyleneadipate),OCN—R—(OCH₂CH₂CH₂CH₂OCO—CH₂C H₂CH₂CH₂—CO)_(x)—R—NCO(polybutyleneadipate), and OCN—R—(OCH₂CH₂CH₂CH₂CH₂CH₂OCO)_(x)—R—NCO(polyhexamethylene-polycarbonate), where in each case, R can be CH₂ orCH₂CH₂ or alkyl.

It is preferred that the one or more polyisocyanates include at leastone diisocyanate (having two reactive isocyanate groups per molecule)and/or at least one triisocyanate (having three reactive isocyanategroups per molecule).

Examples of useful diisocyanates can be found in the text by Ulrich, Id.at pp. 319, 330, 370, 374, and include (with commercial suppliers) HDI(Bayer), 1,5 Diisocyanatopentane, TMDI (Huls), C12DI (duPont),1,6,11-Undecanetriioscyanate (duPont), CHDI (Akzo), BDI (Eastman/Sun),HXDI (Takeda), IPDI (BASF, Bayer, Hüls, Olin), IMCI, DDI-1410 (Henkel),XDI (Takeda), m-TMXDI (American Cyanamid), p-TMXDI (American Cyanamid),DEBI, HMDI (Bayer), OCN(CH₂)₃O(CH₂)₃NCO, OCN(C H₂)₃OCH₂CH₂O(CH₂)₃NCO,OCN(CH₂)3OCH(CH3)CH₂O(CH2)₃NCO, OCN(CH₂)₃O(CH₂)₃O(CH₂)₃NCO,OCN(CH₂)₃O(CH₂)₂O(CH₂)₂O(CH₂)₃NCO, OCN(CH₂)₃OCH(CH₃)CH(CH₃)O(CH₂)₃NCO,OCN(CH₂)₃OCH₂C(CH₃)₂CH₂O(CH₂)₃NCO, OCN(CH₂)₃OCH₂C(Et)₂CH₂O(CH₂)₃NCO,

OCN(CH₂)₃O(CH₂)₄O(CH₂)₃NCO, OCN(CH₂)₃O(CH₂)₆O(CH₂)₃NCO,OCN(CH₂)₃O(CH₂)₁₀O(CH₂)₃NCO, PPDI (Akzo, duPont), 2,4-TDI (Bayer),TDI(80:20) (BASF, Dow, Olin, Rhone-Poulenc, Enichem), MDI (BASF, Bayer,Dow, ICI, Enichem, Mitsui, Toatsu), PMDI (BASF, Bayer, Dow, ICI,Enichem, Mitsui, Toatsu), NDI (Bayer), TODI (Nippon-Soda), and the like.

Blends of of diisocyanates and triisocyanates that are useful in thepresent invention are disclosed in U.S. Pat. No. 5,925,595, to Seitz etal. A preferred diisocyanate is meta-tetramethylenexylylene diisocyanate(TMXDI), and a preferred triisocyanate isN,N′,N″-tris(6-isocyanatohexyl)-nitrodotricarbonic triamide (CAS N.67635-83-0; available as Desmodur N3,200 from Bayer Corporation,Pittsburgh, Pa.). It is more preferred that the polyisocyanates includeboth a diisocyanate and a triisocyanate.

It is believed that the ratio between the number of functional groupssupplied by the diisocyanate and by the triisocyanate has an effect uponthe composition of the polyurea shell and, thus, can be used as acontrollable parameter for obtaining a desired release rate. When TMXDIand N,N′,N″-tris(6-isocyanatohexyl)-nitrodotricarbonic triamide are usedas the diisocyanate and triisocyanate, respectively, a preferred ratiois 1:1.

Polyamines (i.e., polyfunctional amines) that are useful in the presentmethod include any polyamine that is capable of reacting withpolyisocyanates to form polyurea. Suitable amines include, but are notlimited to, diethylene triamine, triethylene tetramine, tetraethylenepentamine, iminobispropylamines, amine epoxy adducts, alkyldiamines fromethylene diamine to hexamethylene diamine, trimethylolpropanetris[poly(propylene glycol)amine terminated] ether (available asJeffamine T-403, CAS No. 39423-51-3) from Texaco Corp. or Aldrich), alldiamines and triamines produced by Texaco Corp. and marketed under thetrade name of Jeffamine, piperazine, isophorone diamine,bis-(4-aminocyclohexyl)methane, 1,2-, 1,3-, and 1,4-cyclohexane diamine,1,2-propane diamine, N,N,N-tris-(2-aminoethyl)-amine, poly(ethyleneimine)s, N-(2-aminoethyl)-piperazine,N,N′-bis-(3-aminopropyl)-ethylenediamine,N,N′-bis-(2-aminoethyl)-1,3-propylenediamine,N,N′-bis-(3-aminopropyl)-1,3-propylenediamine,N,N,N′-tri-(2-aminoethyl)-ethylene diamine,

It is preferred that the one or more polyamines that are used in themethod include at least one triamine and/or at least one tetramine. Infact, it is more preferred that two or more polyamines be used and thatthey be selected from diamines, triamines and tetramines. It is evenmore preferred that both a triamine and a tetramine are included.Preferred triamines include trimethylolpropane tris[poly(propyleneglycol)amine terminated] ether (available as Jeffamine T-403), anddiethylene triamine, and preferred tetramines includetriethylenetetramine (TETA).

When a blend of a triamine and a tetramine is added to the reaction, itis preferred that the ratio of the number of functional groups suppliedby the triamine relative to the number of functional groups supplied bythe tetramine that is used is between about 100:0 to 0:100. As usedherein, this ratio may be referred to as the ratio between the ofequivalents of triamine:tetramine. A ratio of equivalents oftriamine:tetramine of between about 90:10 and 10:90 is more preferred,yet more preferred is a ratio of between about 80:20 and 20:80, evenmore preferred is a ratio of between about 60:40 and 40:60, and yet morepreferred is a ratio of about 50:50.

It has been found that the release rate of an agricultural active in thecore of a microparticle having a polyurea shell, can be modulated byvarying the ratio of the equivalents of a triamine such as JeffamineT-403 and the equivalents of a tetramine such as triethylene tetramine.Accordingly, the parameter of the equivalents ratio of triamine totetramine that is used in the interfacial polymerization reaction is oneof the parameters that can be used to obtain a pre-selected controlledrelease rate of the active.

When the total amount of polyisocyanates and the total amount ofpolyamines that are contacted in the present method are considered, itis preferred that the ratio of the total equivalents of polyisocyanatesto the total equivalents of polyamines is between about 4:1 and 1:4,more preferred is a ratio of 2:1 to 1:2, and yet more preferred is aratio of about 1:1.

It is believed that the temperature at which the polymerization reactiontakes place is a factor in obtaining a fully-formed and intact shell,without pores or other significant irregularities. Accordingly, it ispreferred that the polymerization reaction is carried out at atemperature of between about 25° C. and about 90° C., and more preferredthat the temperature be between about 40° C. and 75° C.

When the novel microcapsules are formed, the thickness of the shell wallcan be controlled by varying the amount of the combined polyisocyanatesand polyamines that are used, relative to the total amount of the liquidorganic phase. The higher the level of polyisocyanates and polyamineswith respect to the amount of the liquid organic phase, the thicker thepolyurea shell wall that will be formed. In this specification the shellwall thickness is expressed in terms of the weight ratio of polyurea tocore material. The weight ratio of the polyurea shell to the core can becontrolled as described above, and desirably falls between about 5:100and about 50:100. It is more preferred that the shell:core weight ratiois between about 10:100 and about 40:100, yet more preferred about15:100 to about 30:100. However, since the thickness of the shell wallhas an effect on the rate of release of an agricultural active from thecore of the microcapsule when it is exposed to natural environmentalconditions, shell wall thickness is a variable that can be controlled toprovide a pre-selected release rate profile.

The terms “natural environmental conditions”, as used herein, are to beunderstood to mean the weather conditions that a microcapsule of thepresent invention will be exposed to when it is applied to a plant, aseed, or to soil, in a conventional soil-based growing environment. Suchconditions include normal ambient rainfall, soil moisture, sunshine,temperature, biological activity, and the like.

When it is said that the agricultural active is released from themicrocapsule at a “pre-selected controlled rate”, the terms“pre-selected controlled rate” refer to a pre-selected release profileof the active from the microcapsules, as can be represented by a plot ofthe cumulative amount of the active that has been released as a functionof the time of exposure. One method of obtaining a microcapsule having apre-selected controlled release rate is to determine the release rate ofthe active from the microcapsule under standardized test conditions(such as are described in detail in the Examples below) and thencorrelating the release profile obtained under standard conditions withthe release profile of the active under normal environmental conditions.One of skill in the art of controlled released pesticides wouldunderstand that after this correlation is made several times, therelease profile determined according to the standardized test methodscan be used to predict the release rate under normal environmentalconditions.

The controlled release forms of the present invention can be of anygeometrical shape, but spherical microcapsules are preferred. Aparticularly useful form of the novel microcapsule includes a polyureashell enclosing a core which comprises silthiopham, where themicrocapsule has an average size of from about 21μ to about 8μ, wherethe weight ratio of the shell to the core is from about 15:100 to about30:100, and where the amount of silthiopham in the core is from about30% to about 60%, by weight.

The microcapsules can be used in any manner in which other controlledrelease forms of agricultural actives are used, and can be applied tothe soil, to seeds, roots, tubers, and any other form of plantpropagation material, as well as to any part of a growing plant.

The subject microcapsules can be used, without limitation, on suchplants as corn, cereals, including wheat, barley, rye, and rice,vegetables, clovers, legumes, including beans, peas and alfalfa,vegetables, sugar cane, sugar beets, tobacco, cotton, rapeseed,sunflower, safflower, and sorghum, and on plant propagation material ofsuch plants.

It is preferred that the microcapsules be used with legumes (members ofthe class Magnoliopsida and the order Fabales). It is more preferredthat the plant be in the family Fabaceae (formerly Leguminosae) and thesub-family Papilionoideae or Faboideae, and even more preferred that theplant be selected from the group consisting of Pisum spp. (including thegarden pea, P. sativum), Medicago spp. (including alfalfa, M. sativa),Arachis spp. (including peanuts, A. hypogaea), soybeans (includingGlycine max, Glycine hispida), Vicia spp. (including vetches), Vignaspp. (including cowpeans), Vicia spp. (including fava bean, V. faba),trefoil, clovers and Phaseolus spp. (including P. vulgaris, P. lunatus,P. limensis, and P. coccineus). It is most preferred that the presentmicrocapsules be used with wheat and soybeans.

The microcapsules can be applied to any type of plant seed as a coating,either neat or with sticking agents or other adjuvants.

When silthiopham is used as the first agricultural active, a preferredapplication is to apply the controlled release microcapsules to theseeds or the soil during the planting of winter wheat in order to obtainprotective activity against Gaeumannomyces graminis in the fall andthroughout the winter, but to retain sufficient activity to provideprotection against renewed biological challenge in the spring.

In those embodiments of the invention where the high melting material isother than an agricultural active, the same general techniques, times,temperatures and concentrations can be used for the preparation ofmicrocapsules that have been described herein for agricultural actives.

The following examples describe preferred embodiments of the invention.Other embodiments within the scope of the claims herein will be apparentto one skilled in the art from consideration of the specification orpractice of the invention as disclosed herein. It is intended that thespecification, together with the examples, be considered to be exemplaryonly, with the scope and spirit of the invention being indicated by theclaims which follow the examples. In the examples all percentages aregiven on a weight basis unless otherwise indicated.

EXAMPLE 1

This example illustrates the production of microcapsules containingsilthiopham as the agricultural active and with the use of a citric acidderivative as an organic solvent.

An aqueous solution of Lomar D surfactant (5.16 g; available from HenkelCorp., Morristown, N.J.) was prepared in 90.4 g water in a 250 mlbeaker. The pH of the solution was adjusted to 7.2 by adding a smallamount of citric acid, and the solution was heated to 55° C. An organicliquid solution was prepared by intermixing silthiopham(N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide, 16.00 g,available from Monsanto Company, St. Louis, Mo.),acetyltri-n-butyl-citrate (34.0 g; available as Citroflex A-4 fromMorflex, Inc., Greensboro, N.C.), Desmodur N 3,200 (7.23 g; an aliphaticpolyisocyanate (tri-isocyanate) based on hexamethylene diisocyanate,available from Bayer Corporation, Pittsburgh, Pa.) andmeta-tetramethylenexylylene diisocyanate (TMXDI) (2.37 g; available fromMiles Laboratories, Inc.) and then heating the mixture until all of thesolids were dissolved. While the temperature of the solution wasmaintained at 50-55° C., the solution was agitated with a SilversonS4RT-4 mixer equipped with a six hole screen for 5-10 seconds at 4,200rpm and the organic solution was added into the agitated solution in 20seconds. The mixture was further agitated at 9,500 to 10,200 rpm for 40seconds. After the formed emulsion was transferred into a 400 ml beakerequipped with a mechanic stirrer set at 625 rpm, an amine solutioncontaining water (5.38 g), triethylenetetramine (m.w. 146.2), (1.10 g)and trimethylolpropane tris[poly(propylene glycol)amine terminated]ether (4.32 g, available as Jeffamine T-403, from Texaco Co. or Aldrich;m.w. ˜440) was added into the emulsion immediately. The temperature ofthe beaker was maintained at 55°-62° C. for 3 hours after which most ofthe isocyanate infrared absorbance peak at 2270 cm⁻¹ haddisappeared—indicating reaction of the isocyanate. A light yellow slurry(118 g) was collected. The average particle size was 4.2 microns. Theweight ratio between wall and core was 30:100 and the amount ofsilthiopham in the core was 32% by weight.

EXAMPLE 2

This example illustrates the production of microcapsules containingsilthiopham having thinner shells than in Example 1.

An aqueous solution of Lomar D (5.16 g) was added to 90.4 g water in a250 ml beaker, and the pH of the solution was adjusted to 7.2 by addinga small amount of citric acid and the solution was heated to 55° C. Anorganic solution was prepared by intermixing silthiopham (16.00 g),Citroflex A-4 (34.0 g), Desmodur N 3,200 (4.82 g) and TMXDI (1.58 g) andthen heating the mixture until all of the solids dissolved and thetemperature of the solution was maintained at 50°-55° C. The aqueoussolution was agitated with a Silverson S4RT-4 mixer equipped with a sixhole screen for 5-10 seconds at 4,200 rpm and the organic solution wasadded to the agitated solution in 20 seconds. The mixture was furtheragitated at 9,500 to 10,200 rpm for 40 seconds. After the formedemulsion was transferred into a 400 ml beaker equipped with a mechanicstirrer set at 625 rpm, an amine solution containing water (5.38 g),triethylenetetramine (0.73 g) and Jeffamine T403 (2.88 g) was added intothe emulsion immediately. The temperature of the beaker was remained at55°-62° C. for 2 hours. The isocyanate infrared absorbance peak at 2270cm⁻¹ disappeared. 114 g of light yellow slurry was collected. Theaverage particle size was 4.21 micron. The weight ratio between wall andcore of the particles was 20:100 and the amount of active in the corewas 32% by weight.

EXAMPLE 3

This illustrates the formation of microcapsules containing a higherlevel of silthiopham in the core.

An aqueous solution of Lomar D (5.16 g) was prepared by adding thesurfactant to 90.4 g water in a 250 ml beaker. The pH of the solutionwas adjusted to 7.2 by adding a small amount of citric acid and heatedto 55° C. An organic solution was prepared by mixing silthiopham (16.00g), Citroflex A-4 (34.0 g), Desmodur N 3,200 (7.23 g) and TMXDI (2.37 g)together and then heating the mixture until all of the solids weredissolved and the temperature of the solution was maintained at 50°-55°C. The aqueous solution was agitated with a Silverson S4RT-4 mixerequipped with a six hole screen for 5-10 seconds at 4,200 rpm and theorganic solution was added into the agitated solution in 20 seconds. Themixture was further agitated at 9,500 to 10,200 rpm for 40 seconds.After the formed emulsion was transferred into a 400 ml beaker equippedwith a mechanic stirrer set at 625 rpm, an amine solution containingwater (5.38 g), triethylenetetramine (1.10 g) and Jeffamine T-403 (4.32g) was added into the emulsion immediately. The temperature of thebeaker was remained at 55°-62° C. for 3 hours. Most of the isocyanateinfrared absorbance peak at 2270 cm⁻¹ disappeared. 118 g of light yellowslurry was collected. The average particle size was 4.2 micron. Theweight ratio between wall and core was 30:100 and the amount of activein the core was 40% by weight.

EXAMPLE 4

This illustrates the preparation of microcapsules containing silthiophamhaving 20:100 wall:core weight ratio and 40% by weight active in thecore.

An aqueous solution of Lomar D (5.16 g) was prepared by adding thesurfactant to 90.4 g water in a 250 ml beaker. The pH of the solutionwas adjusted to 7.2 by adding a small amount of citric acid and thesolution was heated to 55° C. An organic solution was prepared by mixingsilthiopham (20.00 g), Citroflex A-4 (30.0 g), Desmodur N 3,200 (4.64 g)and TMXDI (1.74 g) together and then heating the mixture until all ofthe solids were dissolved and the temperature of the solution wasmaintained at 50°-55° C. The aqueous solution was agitated with aSilverson S4RT-4 mixer equipped with a six hole screen for 5-10 secondsat 4,200 rpm and the organic solution was added into the agitatedsolution in 20 seconds. The mixture was further agitated at 9,500 to10,200 rpm for 40 seconds. After the formed emulsion was transferredinto a 400 ml beaker equipped with a mechanic stirrer set at 625 rpm, anamine solution containing water (4.00 g), triethylenetetramine (0.74 g)and Jeffamine T-403 (2.90 g) was added into the emulsion immediately.The temperature of the beaker was maintained at 55°-62° C. for 2.5hours. The isocyanate infrared absorbance peak at 2270 cm⁻¹ disappeared.118 g of light yellow slurry was collected. The average particle sizewas 4.5 micron. The weight ratio between the wall and core was 20:100and the amount of active in the core was 40%.

EXAMPLE 5

This illustrates the production of microcapsules containing silthiophamwhere the capsules have a 15:100 weight ratio of wall:core.

Microcapsules were produced by the method described in Example 4, exceptthat the organic solution contained 3.61 g of Desmodur N 3,200 and 1.19g of TMXDI, and the amine solution contained 3.0 g of water, 0.55 g oftriethylenetetramine and 2.16 g of Jeffamine T-403.107 g of a lightyellow product was collected and the average particle size was 3.4microns. The weight ratio between the wall and the core was 15:100 andthe amount of silthiopham in the core was 40% by weight.

EXAMPLE 6

This illustrates the effect of the wall thickness of microcapsules onthe release rate of silthiopham into water.

Microcapsules containing silthiopham were produced by the methoddescribed in Examples 3-5, except that the ratio of equivalents ofDesmodur N3,200 and TMXDI was maintained at 2:1, and the ratio of totalisocyanate functional groups to total amine functional groups wasmaintained at 1:1 so that the polymerization reaction wasstoichiometrically balanced. Microcapsules having wall:core weightratios of 15:100, 20:100 and 30:100 were then prepared, and theproperties of these microcapsules are shown in Table 1. The release rateof silthiopham was measured as described below. TABLE 1 Properties ofmicrocroencapsulated silthiopham. Wall:Core Ratio of Avg. ParticleSample Weight Ratio TETA:T-403^(a) size (microns) % REA 1 15:100 50:503.5μ 1.5% 2 20:100 50:50 3.7μ 1.2% 3 30:100 50:50 4.5μ 0.5%

Notes:

a. Ratio of TETA:T-403 is equivalents of TETA:equivalents of T-403.

The release rate of an agricultural active from a controlled releaseformulation was measured by placing the controlled release formulationin a water sink so that at 100% release the total active present is lessthan approximately one third the water solubility level. The releasesolution is then agitated by shaking or stirring. At intervals, analiquot is removed. The aliquot is filtered to separate the controlledrelease matrix from active dissolved in water. The filtered aliquot isthen assayed for active present. Release curves are plotted to showhours after start of experiment vs percent of total active released.

When the release rate of microcapsules having a polyurea shell, or wall,enclosing a core containing silthiopham was tested, the followingprocedure was followed:

Release Solution Preparation:

Prepare 450 mL of a solution of the formulation containing a target of10-12 ppm silthiopham (silthiopham water solubility is 35 ppm at 20°C.).

Note time of start.

Immediately invert solution approximately 100 times and take an aliquot.

Agitate by shaking on a platform shaker.

Separation of Dissolved Active from Controlled Release Matrix:

Note time.

Take an aliquot immediately after shaking (the level of active in thissample is reported as the percentage of readily extractable active (%REA), which is believed to represent the relative amount of active thatwas not enclosed in the microcapsules, or was present on the surface ofthe microcapsules).

Filter with a 0.45 micron PTFE filter-discarding first 3 mL.

Assay filtered aliquot by HPLC.

HPLC Methodology (Reverse Phase; UV):

-   Column: Alltech Alltima C18; 5 micron particle size; (250×4.5 mm)-   Flow: 1.2 mL/min-   Injection volume: 100 microliters-   Detector: UV; 220 nanometers (Varian 9050)-   Mobile phase A: 12.6 g K₂HPO₄+3600 mL water to pH 6.4 with 85%    H₃PO₄. Add 400 mL methanol.-   Mobile phase B: Methanol-   Mobile phase: 22% A; 78% B-   Approximate retention time: 6 to 7 minutes-   Standard range: 0.15 to 15 ppm silthiopham.

Release rates of the microcapsule products of Samples 1-3 were measuredas described above and the results are shown in FIG. 1. As can be seen,less than 10% of the silthiopham was released from sample 3 (having30:100 wall:core ratio) after 1,500 hours, and the release rateincreased as the wall:core ratio (essentially a measure of the thicknessof the polyurea shell) decreased. This showed that the release ratecould be modulated by controlling the wall:core ratio and that almostall of the active was present in the cores of the microcapsules. It wasobserved, however, that the release rate of each of the three sampleswas relatively low.

Microcapsules were prepared by the same methods as described in Examples3-5, except that the amount of silthiopham that was loaded into the corewas varied to provide silthiopham loadings of 50% and 60%, by weight, ofthe core. The wall:core ratio for the microcapsules was varied from15:100, 20:100 and 30:100, as described above in Example 6. The releaserates of each of the microcapsules having different silthiopham loadingrates were measured and the results are shown in FIG. 2 for the 50%loading, and FIG. 3 for the 60% loading. In general, it can be seen thatthe higher the active loading in the core, the more rapid the releaserate, while thicker shell walls give lower release rates, as would beexpected.

EXAMPLE 7

This illustrates the effect of the amount of active in the core of themicrocapsules on the release rate of silthiopham into water.

Microcapsules containing silthiopham were produced by the methoddescribed in Example 6, except that the wall:core ratio was maintainedat 30:100, while the loading of silthiopham in the core was varied from32% to 60%, by weight. Also, the reaction mixture was intermixed by theuse of a Waring blender, rather than with a Silverson mixer. When theWaring blender was used, it was found that, in general, smallermicrocapsules could be formed than when the Silverson mixer was used.

A 500 ml Waring blender was connected to a 0-140 volt Variac voltagecontroller to provide speed control. The aqueous solution was placed inthe blender and mixed at a Variac setting of 30/140 V during theaddition of the organic solution—over a period of about 20 seconds.After the organic solution had been added, the Variac was increased to140/140 V to provide maximum speed for 40 seconds. The speed was thenreduced to a 20/140 V Variac setting for the addition of the aminemixture. This took approximately one minute, after which the mixture wasimmediately transferred to a beaker being stirred at about 250-450 rpmby an overhead stirrer for the duration of the reaction.

The properties of the microcapsules are shown in Table 2. TABLE 2Properties of microcapsules containing silthiopham. Amount of Active incore Ratio of Avg. Particle Sample (% by weight) TETA:T-403^(a) size(microns) % REA 4 32% 50:50 2.4μ 1.4% 5 50% 50:50 2.4μ 5.0% 6 60% 50:502.2μ 3.8%

Notes:

a. Ratio of TETA:T-403 is equivalents of TETA to equivalents of T-403.

The release rate of silthiopham from the microcapsules was measured asdescribed in Example 6, and the results are shown in FIG. 4. It is seenthere that the sample having the highest level of silthiopham in thecore provided the fastest release rate, with release rate decreasing asthe level of silthiopham in the core decreased. All microcapsules werestill releasing after 1,200 hours (50 days). This showed that therelease rate could be modulated by controlling the amount of activeinitially placed in the core of the microcapsules.

Microcapsules having 15:100 and 20:100 shell:core ratios were alsoproduced by the same methods and each had silthiopham loadings of 32%,50% and 60% by weight in the core. Release rates for these samples werealso measured as described in Example 6, and the results are shown inFIG. 5 for microcapsules having 15:100 shell:core ratio and in FIG. 6for 20:100 shell:core ratio. It can be seen that the release rate can bemodulated by varying the shell:core ratio and by varying the loading ofthe active in the core. In general, the thicker the shell wall, theslower the release rate, while the higher the loading of active in thecore, the faster the release rate.

EXAMPLE 8

This example illustrates the effect of particle size on the release rateof silthiopham from microcapsules having polyurea shells.

Microcapsules were prepared by the methods described in Example 6,except that the wall:core ratio was maintained at 30:100 and the loadingof silthiopham in the core was maintained at 32% by weight. The averageparticle size was varied from 2.4μ (Sample 7—processed in a Waringblender as in Example 7) to 4.2μ (Sample 8—processed by a Silversonmixer as in Example 1). The release rate of silthiopham was measured asdescribed in Example 6, and the results are shown in FIG. 7. As can beseen from that figure, as the microcapsule size increases, the releaserate decreases. It was also seen that the initial release rate washigher for the smaller particles (5% REA for the 2.4μ particles versusless than 1% REA for the 4.2μ particles). This test was repeated formicrocapsules that were formed by the same method, but had a shell:coreratio of 20:100, 32% loading of silthiopham in the core, and particlesizes of 2.1μ and 4.1μ. Release rates of silthiopham were measured forthese particles by the same methods and the release curves are shown inFIG. 8.

The data from both curves shows that the release rate of the active canbe modulated by controlling the size of the microcapsule. It is believedthat size can be controlled by, for example, control on the shearseverity and duration during blending of the aqueous and organic phaseliquid, and by controlling the temperature and the viscosity of the twophases. It is believed that microcapsules between about 2μ and about 8μare preferred for the present applications, although both larger andsmaller microcapsules are possible.

EXAMPLE 9

This example illustrates the effect of the composition of the shell wallon the release rate of silthiopham from microcapsules having polyureashells.

In this set of experiments, microcapsules were produced by the methodsdescribed in Example 6, except that the wall:core weight ratio wasmaintained at 20:100 and the loading of silthiopham in the core wasmaintained at 50% while the amount of Jeffamine T-403 used in thereaction was increased from 0 to 100%, and a Waring blender was used formixing as described in Example 7. Properties of the resultingmicrocapsules are summarized in Table 3. The average particle size forall of the samples ranged from 2.2 to 2.4 microns, which indicated thatthe ratio of TETA and Jeffamine T-403 did not significantly effect theaverage particle size. In fact, the average particle size of themicrocapsule was found to depend on (1) the agitation during blending ofthe aqueous and organic liquids, (2) the viscosity of the dispersed oremulsified organic phase which contains the active, the solvent, and theisocyanates and (3) the emulsifier or the dispersion reagent. Theinitial release is associated with the composition of the shell. As canbe seen from the data in Table 3, the initial release remained at 0.6%level when the ratio between the equivalents of TETA and the equivalentsof Jeffamine T-403 was below 50%/50%. However the initial release ofsilthiopham was increased from 1.4% to even 17% when the ratio betweenTETA and Jeffamine T-403 was decreased from 50%/50% to 0/100%. Thisresult agrees with the release profiles of silthiopham in water, whichare shown in FIG. 9 where it is seen that the release rate decreaseswhen the concentration of TETA in the in the polymerization reactionincreases, i.e., when the equivalents ratio between TETA and JeffamineT-403 increases. When 100% of Jeffamine T-403 was used, silthiopham wasreleased into water most rapidly. Whereas, when 100% of TETA was used,the release of silthiopham was extremely slow and less than 10% ofsilthiopham was released even after 300 hours. According to the chemicalstructures of both amines, the Jeffamine T-403 molecule with a molecularweight of 440 has three amine groups whereas TETA with a molecularweight of 162 has four amine groups.

This experiment was repeated with microcapsules having shell:core ratiosof 30:100, rather than 20:100, and the effect of varying the TETA/T-403ratio on the release rate was found to be the same as for the thinnercapsule wall. The release rate results for the microcapsules having a30:100 shell:core ratio are shown in FIG. 10 for 10/90 and 50/50TETA/T-403 ratios. As expected, the release rates for the thicker-wallmicrocapsules was slower than for the thinner wall capsules.

In general an amine group in the polyamine molecule will react with anisocyanate to give polyurea. In this process the reaction occurs at theinterface of the organic droplet and the aqueous solution, and a shellcomposed of polyurea forms. It is believed that the density or thepermeability of the shell will depend on the composition of thepolyurea. Since TETA with four amine groups is a much smaller moleculethan Jeffamine T-403 with three amine groups, it is believed that thepolyurea shell made with higher TETA concentration will have the morecondensed shell therefore provide slower release rate of silthiopham.Therefore, the results show that the release profiles of silthiopham inwater can be controlled by varying the ratios of TETA and JeffamineT-403 used during the polymerization. TABLE 3 Properties ofmicroencapsulated silthiopham. Wall Particle Sample ThicknessTETA/T403^(a) Size REA  9 20%     0/100% 2.2μ   17% 10 20% 20%/80% 2.2μ 4.9% 11 20% 40%/60% 2.2μ  2.4% 12 20% 50%/50% 2.4μ  1.4% 13 20% 60%/40%2.2μ 0.60% 14 20% 80%/20% 2.3μ 0.50% 15 20% 100%/0%  2.2μ 0.66%

Notes:

a. The ratio of TETA/T-403 is given as equivalents of TETA perequivalent of T-403.

EXAMPLE 10

This illustrates the stability of microencapsulated silthiopham.

The stability of the encapsulated silthiopham products was studied bymeasuring the initial release of silthiopham in the products after theyhad aged for a certain period after synthesis. As can be seen in Table4, the stability of the microcapsules varies somewhat betweenmicrocapsules having different synthesis parameters, but is, in general,acceptable for a commercially useful product. The initial release ofSample 8 was slightly increased to 1.8% from 0.95% after 81 days.However the initial release of Sample 1 was increased to 11% from 1.5%after 52 days. TABLE 4 Summary of the stability of differentmicrocapsules. Time Time Time (Days) REA (days) REA (Days) REA Sample 13 1.5% 52  11% Sample 2 4 1.2% 53 4.8% Sample 8 4 0.95%  32 1.1% 81 1.8%Sample 16 12 2.6% 54 6.7% 66 6.4%

EXAMPLE 11

This illustrates a study of the microcapsules of the present inventionby scanning electron microscope.

A sample of microcapsules containing silthiopham in the core wasproduced by the methods described in Example 6, except that the capsuleshad a 50% loading of silthiopham in the core with a shell wall:coreratio of 30:100, and mixing was carried out in a Waring blender asdescribed in Example 7. The average particle size as measured by aCoulter counter was 2.4 microns, which is very close to what is observedby a scanning electron micrograph, which is shown in FIG. 11. Themicrocapsules have a spherical shape with some small dimples on thesurface. Since the cores of these microcapsules contain 50% ofsilthiopham, the encapsulated active imposed some stress on the shelland thus the small dimple is believed to be associated with the stressappeared.

The sample shown in FIG. 12 has a 32% loading of silthiopham in the corewith a shell wall:core ratio of 30:100. The average particle size asmeasured by a Coulter counter for this sample was 4.2 microns, whichagrees with the size indicated by the SEM 5 μm bar. The microcapsuleshave a spherical shape and smooth surface. However the small dimplesthat were observed on the capsules of FIG. 11 were not observed on thesurface of these capsules, and only one large dimple was observed on oneof the microcapsules. Since this sample has a only 32% of silthiopham inthe core, the stress from silthiopham on the shell is believed to bemuch smaller than for the capsules having higher levels of silthiopham.

EXAMPLE 12

This example illustrates the formation of a eutectic mixture withsilthiopham and tebuconazole.

The melting temperature at one atmosphere was measured for puresilthiopham and for pure tebuconazole and for mixtures of 10:90, 20:80,30:70, 40:60, 50:50, 60:40, 70:30, 80:20, and 90:10silthiopham:tebuconazole, on a weight basis. The results are shown inFIG. 13, and indicate that the silthiopham/tebuconazole mixture forms aeutectic at about a 50:50 blend. The eutectic melting point appeared tobe somewhat under 50° C., whereas the melting point of pure silthiophamis about 86° C. and the meting point of pure tebuconazole is somewhatover 100° C. This indicates that the eutectic mixture had a meltingpoint that was over 35° C. lower than that of the lowest melting purecomponent (silthiopham, in this case).

EXAMPLE 13

This example illustrates the formation of a eutectic mixture withsilthiopham and simeconazole.

The melting temperature at one atmosphere was measured for puresilthiopham and for pure simeconazole and for mixtures of the twomaterials as described in Example 12. The results are shown in FIG. 14,and indicate that the silthiopham/simeconazole mixture forms a eutecticat a blend somewhere between 100:0 and 60:40, by weight. However, whenthe blend ratio was dropped to below about 50:50, by weight, two meltingpoints were observed. The eutectic melting point appeared to be somewhatunder 70° C., whereas the melting point of pure silthiopham is about 86°C. and the meting point of pure simeconazole is about 118° C. Thisindicates that the eutectic mixture had a melting point that was about16° C. lower than that of the lowest melting pure component(silthiopham, in this case).

EXAMPLE 14

This example illustrates the formation of a eutectic mixture withsilthiopham and 1-(4-fluorophenyl)-2-(1H-1,2,4-triazole-1-yl)-ethanone.

The melting temperature at one atmosphere was measured for puresilthiopham and for pure1-(4-fluorophenyl)-2-(1H-1,2,4-triazole-1-yl)-ethanone and for mixturesof 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, and 90:10silthiopham: 1-(4-fluorophenyl)-2-(1H-1,2,4-triazole-1-yl)-ethanone, ona weight basis. The results are shown in FIG. 15, and indicate that thesilthiopham/1-(4-fluorophenyl)-2-(1H-1,2,4-triazole-1-yl)-ethanonemixture forms a eutectic at a mixture somewhere between 100:0 and 60:40,by weight. The eutectic melting point appeared to be somewhat under 80°C., whereas the melting point of pure silthiopham is about 86° C. andthe meting point of pure1-(4-fluorophenyl)-2-(1H-1,2,4-triazole-1-yl)-ethanone is about 128° C.This indicates that the eutectic mixture had a melting point that wasabout 6° C. lower than that of the lowest melting pure component(silthiopham, in this case).

EXAMPLE 15

This example illustrates the production of microcapsules containingsilthiopham and tebuconazole in the core and where the method is free ofthe use of a solvent.

An aqueous solution was prepared by adding Lomar D (5.16 g) to 90.4 gwater in a 250 ml beaker, and the pH of the solution was adjusted to 7.2by adding a small amount of citric acid. The solution was heated to 65°C. An organic liquid solution was prepared by intermixing silthiopham(25.00 g), tebuconazole (25.00 g), Desmodur N 3,200 (4.82 g) and TMXDI(1.58 g) and then heating the mixture until the solids were dissolvedand the temperature of the solution was maintained at 65°-70° C. Theaqueous solution was agitated with a Silverson S4RT-4 mixer equippedwith a six hole screen for 5-10 seconds at 4,200 rpm and the organicsolution was added into the agitated solution in 20 seconds. The mixturewas further agitated at 9,500 to 10,200 rpm for 40 seconds. After theformed emulsion was transferred into a 400 ml beaker equipped with amechanic stirrer set at 625 rpm, an amine solution containing water(4.00 g), triethylenetetramine (0.73 g) and Jeffamine T-403 (2.88 g) wasadded into the emulsion immediately. After maintaining the temperatureof the mixture at 65°-70° C. for 0.5 hour, the isocyanate infraredabsorbance peak at 2270 cm⁻¹ disappeared. 108.3 g of yellow slurry wascollected after 1 hour. The weight ratio between the wall and the corewas 20:100.

EXAMPLE 16

This illustrates the production of microcapsules containing silthiophamand tebuconazole in the absence of a solvent, but with a higherwall:core ratio that in Example 15.

Microcapsules were produced by the method described in Example 15,except that the organic solution contained 7.23 g of Desmodur N 3,200and 2.37 g of TMXDI, and the amine solution contained 6.0 g of water,1.1 g of triethylenetetramine and 4.32 g of Jeffamine T-403. Theisocyanate peak at 2270 cm⁻¹ disappeared after 1.5 hours, and 107 g of alight yellow product was collected after 2 hours. The weight ratiobetween the wall and the core was 30:100.

EXAMPLE 17

This illustrates the production of microcapsules containing silthiophamand tebuconazole in the absence of a solvent, but with a higherwall:core ratio that in Example 15 and with only one type of amine.

Microcapsules were produced by the method described in Example 15,except that the organic solution contained 9.22 g of Desmodur N 3,200and 3.03 g of TMXDI, and the amine solution contained 6.0 g of water,2.8 g of triethylenetetramine (TETA) and no Jeffamine T-403. Theisocyanate peak at 2270 cm⁻¹ disappeared after 2 hours, and 133 g of alight yellow product was collected after 2.25 hours. The weight ratiobetween the wall and the core was 30:100.

The product appears as a light yellow slurry and no crystals can beobserved in the product under optical microscopy. The images fromscanning electron microscopy (SEM) suggest that spherical microcapsuleswere formed.

EXAMPLE 18

This example illustrates the use of microcapsules formed according tothe present invention to form a coating on wheat seed.

Wheat seed (100 g, of the species triticum aestivum, var. “Consort”) wasplaced into the bowl of a Hege 11 seed coating machine. A sample (0.2ml) of a formulation prepared according to the procedure of Example 1,but having a polyurea shell wall thickness of 30%, a concentration ofsilthiopham in the core of 60%, by weight, and an amine ratio betweenTETA and Jeffamine T403 of 50:50. This sample was diluted with water(0.8 ml) to afford a formulation with a silthiopham concentration of 125g/1000 ml. This formulation was applied via syringe into the turningHege bowl filled with wheat (100 g). The Hege bowl was turned on for 30sec to provide uniform distribution and coating of seeds.

EXAMPLE 19

This example illustrates the use of microcapsules formed according tothe present invention to form a coating on wheat seed.

The same procedure as described in Example 18 was used to coat wheatseed, except that 0.012 ml of Vinamul 18132 was added to the formulationcontaining the silthiopham. Wheat seed coated with the microcapsules ofthe present invention were obtained.

All references cited in this specification, including without limitationall papers, publications, patents, patent applications, presentations,texts, reports, manuscripts, brochures, books, internet postings,journal articles, periodicals, and the like, are hereby incorporated byreference. The discussion of the references herein is intended merely tosummarize the assertions made by their authors and no admission is madethat any reference constitutes prior art. Applicants reserve the rightto challenge the accuracy and pertinency of the cited references.

In view of the above, it will be seen that the several advantages of theinvention are achieved and other advantageous results obtained.

As various changes could be made in the above methods and compositionswithout departing from the scope of the invention, it is intended thatall matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense.

1-91. (canceled)
 92. A method of modulating the release rate of anagricultural active from a microcapsule containing the agriculturalactive to obtain a pre-selected controlled release rate of the active,the method comprising providing an organic liquid composition comprisingthe agricultural active; forming the liquid composition into smalldroplets; enclosing each droplet in a non-water soluble shell to form amicrocapsule by dispersing the small droplets of the organic liquidcomposition in an aqueous liquid which is immiscible with the organicliquid composition; and forming a non-water soluble shell by interfacialpolymerization at the interface of the droplets and the aqueous liquidwhich shell encloses each droplet as a core of a microcapsule, whereinthe shell is designed to release the agricultural active from themicrocapsule at a pre-selected controlled rate when the microcapsule isexposed to natural environmental conditions.
 93. The method according toclaim 92, wherein the organic liquid composition comprises one or morepolyisocyanates; the aqueous liquid comprises one or more polyamines;and wherein the interfacial polymerization comprises reaction of thepolyisocyanates and the polyamines at the interface of the droplets andthe aqueous liquid.
 94. The method according to claim 93, wherein theone or more polyisocyanates comprise 1,12-dodecane diisocyanate,cyclobutane-1,3-diisocyanate, cyclohexane-1,3-diisocyanate, 2,4- and/or2,6-hexahydrotoluylene diisocyanate, 4,4′,4″-triphenylmethanetriisocyanate, tris-(4-isocyanatophenyl)-thiophosphate, Desmodur N3300(CAS 104559-01-5; 1,6-diisocyanate homo-polymer),OCN—R—(O—CH₂CH₂)_(x)—R—NCO (polyethylene glycol),OCN—R—(OCH₂—CH—CH₃)_(n)—R—NCO (polypropylene glycol),OCN—R—(OCH₂CH₂CH₂CH₂)_(x)—R—NCO (polytetramethylene glycol),OCN—R—(OCH₂CH₂OCO—CH₂CH₂CH₂CH₂—CO)_(x)—R—NCO (polyethyleneadipate),OCN—R—(OCH₂CH₂CH₂CH₂OCO—CH₂CH₂CH₂CH₂—CO)_(n)—R—NCO(polybutyleneadipate), OCN—R—(OCH₂CH₂CH₂CH₂CH₂CH₂OCO)_(x)—R—NCO(polyhexamethylene-polycarbonate), where in each case, R can be CH₂ orCH₂CH₂ or alkyl, HDI, 1,5 Diisocyanatopentane, TMDI, C12DI,1,6,11-Undecanetriioscyanate, CHDI, BDI, HXDI, IPDI, IMCI, DDI-1410,XDI, m-TMXDI, p-TMXDI, DEBI, HMDI, OCN(CH₂)₃O(CH₂)₃NCO,OCN(CH₂)₃OCH₂CH₂O(CH₂)₃NCO, OCN(CH₂)3OCH(CH3)CH₂O(CH2)₃NCO,OCN(CH₂)₃O(CH₂)₃O(CH₂)₃NCO, OCN(CH₂)₃O(CH₂)₂O(CH₂)₂O(CH₂)₃NCO,OCN(CH₂)₃OCH(CH₃)CH(CH₃)O(CH₂)₃NCO, OCN(CH₂)₃OCH₂C(CH₃)₂CH₂O(CH₂)₃NCO,OCN(CH₂)₃OCH₂C(Et)₂CH₂O(CH₂)₃NCO,

OCN(CH₂)₃O(CH₂)₄O(CH₂)₃NCO, OCN(CH₂)₃O(CH₂)₆O(CH₂)₃NCO,OCN(CH₂)₃O(CH₂)₁₀O(CH₂)₃NCO, PPDI, 2,4-TDI, TDI(80:20), MDI, PMDI, NDI,TODI, and mixtures thereof.
 95. The method according to claim 93,wherein the one or more polyisocyanates are selected from the groupconsisting of N,N′,N″-tris(6-isocyanatohexyl)-nitrodotricarbonictriamide and meta-tetramethylenexylylene diisocyanate.
 96. The methodaccording to claim 95, wherein the one or more polyisocyanates compriseN,N′,N″-tris(6-isocyanatohexyl)-nitrodotricarbonic triamide andmeta-tetramethylenexylylene diisocyanate.
 97. The method according toclaim 93, wherein the one or more polyamines comprise a polyamineselected from the group consisting of diethylene triamine, triethylenetetramine, tetraethylene pentamine, iminobispropylamines, amine epoxyadducts, alkyldiamines from ethylene diamine to hexamethylene diamine,and trimethylolpropane tris[poly(propylene glycol)amine terminated]ether.
 98. The method according to claim 93, wherein the one or morepolyamines comprise at least two polyamines selected from the groupsconsisting of diamines, triamines and tetramines.
 99. The methodaccording to claim 93, wherein the one or more polyamines comprise atleast one triamine and at least one tetramine.
 100. The method accordingto claim 99, wherein the release rate of the active is modulated bycontrolling the ratio of the equivalents of triamine to the equivalentsof tetramine.
 101. The method according to claim 93, wherein the one ormore polyamines are selected from the group consisting of diethylenetriamine, tetraethylene pentamine, triethylene tetramine,iminobispropylamines, amine epoxy adducts, alkyldiamines from ethylenediamine to hexamethylene diamine, and trimethylolpropanetris(poly(propylene glycol)amine terminated) ether.
 102. The methodaccording to claim 93, wherein the one or more polyamines are selectedfrom the group consisting of triethylenetetramine and trimethylolpropanetris[poly(propylene glycol)amine terminated] ether.
 103. The methodaccording to claim 93, wherein the one or more polyamines comprisetriethylenetetramine and trimethylolpropane tris(poly(propyleneglycol)amine terminated) ether.
 104. The method according to claim 93,wherein the aqueous liquid comprises water.
 105. The method according toclaim 93 wherein the reaction of the one or more polyisocyanates withthe one or more polyamines is carried out at a temperature of betweenabout 25° C. and about 90° C.
 106. The method according to claim 93wherein the reaction of the one or more polyisocyanates and the one ormore polyamines is carried out at a temperature of between about 40° C.and about 75° C.
 107. The method according to claim 93 wherein the ratioof the equivalents of polyisocyanates to the equivalents of polyaminesis between about 4:1 to about 1:4.
 108. The method according to claim 93wherein the ratio of the equivalents of polyisocyanates to theequivalents of polyamines is between about 2:1 to about 1:2.
 109. Themethod according to claim 93, wherein the ratio of the equivalents ofpolyisocyanates to the equivalents of polyamines is about 1:1.
 110. Themethod according to claim 100, wherein the one or more polyaminesomprise at least one triamine and at least one tetramine present in anequivalents ratio of triamine:tetramine of from about 100:0 to about0:100.
 111. The method according to claim 100, wherein the one or morepolyamines comprise at least one triamine and at least one tetraminepresent in an equivalents ratio of triamine:tetramine of from about20:80 to about 80:20.
 112. The method according to claim 100, whereinthe one or more polyamines comprise at least one triamine and at leastone tetramine present in an equivalents ratio of triamine:tetramine offrom about 40:60 to about 60:40.
 113. The method according to claim 100,wherein the one or more polyamines comprise at least one triamine and atleast one tetramine present in an equivalents ratio oftriamine:tetramine of from about 50:50.
 114. The method according toclaim 93, wherein an emulsifier is also present.
 115. The methodaccording to claim 114, wherein the emulsifier is selected from amaterial comprising a sodium salt of naphthalene sulfonic acidformaldehyde polymer and a sodium salt of maleic acid-olefin copolymer.116. The method according to claim 93, wherein the pH of the solution isadjusted to between about 4 and about 11 by the addition of citric acid.117. The method according to claim 93, wherein the pH of the solution isadjusted to between about 5 and about 9 by the addition of citric acid.118. The method according to claim 93, wherein the pH of the solution isadjusted to between about 7 and about 8 by the addition of citric acid.119. The method according to claim 92, wherein the weight ratio of theshell to the core is from about 5:100 to about 50:100.
 120. The methodaccording to claim 92, wherein the weight ratio of the shell to the coreis from about 10:100 to about 40:100.
 121. The method according to claim92, wherein the weight ratio of the shell to the core is from about15:100 to about 30:100.
 122. The method according to claim 92, whereinthe microcapsules have an average particle size of from 1μ to 20μ. 123.The method according to claim 92, wherein the microcapsules have anaverage particle size of from 2μ to 10μ.
 124. The method according toclaim 92, wherein the microcapsules have an average particle size offrom 2μ to 6μ.